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1.  Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients 
Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study utilized an employment-based reinforcement intervention to promote opiate and cocaine abstinence among opioid-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n=46) were randomly assigned to an Abstinence & Work group that was required to provide negative urine samples in order to enter the workplace and earn incentives for work (n=16), a Work Only group that was permitted to enter the workplace and earn incentives independent of drug use (n=15), and a No Voucher control group that did not receive any incentives for working (n=15) over a 26-week period. The primary outcome was urinalysis-confirmed opiate, cocaine, and combined opiate/cocaine abstinence. Participants were 78% male and 89% African American. Results showed no significant between-group differences in urinalysis-verified drug abstinence or HIV risk behaviors during the 6-month intervention. The Work Only group had significantly greater workplace attendance and worked more minutes per day when compared to the No Voucher group. Several features of the study design, including the lack of an induction period, setting the threshold for entering the workplace too high by requiring immediate abstinence from several drugs, and increasing the risk of relapse by providing a brief detoxification that was not supported by any continued pharmacological intervention, likely prevented the workplace from becoming established as a reinforcer that could be used to promote drug abstinence. However, increases in workplace attendance have important implications for adult training programs.
PMCID: PMC4332775  PMID: 24490712
HIV; contingency management; therapeutic workplace; incentive; injection drug use
2.  [No title available] 
PMCID: PMC3926100  PMID: 24188170
3.  [No title available] 
PMCID: PMC4019046  PMID: 24490711
4.  Acute and chronic administration of a low-dose combination of topiramate and ondansetron reduces ethanol’s reinforcing effects in male Alcohol Preferring (P) rats 
Topiramate (a GABA/glutamate modulator) and ondansetron (a serotonin-3 antagonist) have shown promise as treatments for alcohol use disorders (AUDs), although efficacy is modest/variable for both medications. We recently showed in animal models of consumption and relapse that acute treatment with a combination of these medications was more efficacious than either alone. To determine whether the mechanism for its beneficial effects is through modulation of ethanol’s reinforcing effects, we measured the effect of this combination in male alcohol preferring (P) rats (N=22) responding for ethanol under a progressive-ratio (PR) schedule. Low doses, which either do not affect (ondansetron; 0.001 mg/kg) or only modestly affect (topiramate; 10 mg/kg) alcohol-related behaviors on their own, were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. In addition to acute treatment (1 day), the effects of chronic administration (10 days) were examined in an attempt to model human treatment approaches. The effects of the combination were compared to the low dose of topiramate alone hypothesizing that the combination would be more efficacious than topiramate alone. While both topiramate and the combination similarly reduced PR responding for ethanol following acute treatment and during the initial phase of chronic treatment (days 1–5), after repeated administration (days 6–10), only the combination produced a sustained reduction in ethanol-maintained responding. These results suggest an advantage of the combination over topiramate alone at producing a sustained reduction in ethanol’s reinforcing effects following prolonged treatment, and lend further support for its use as a potential treatment for AUDs.
PMCID: PMC4292872  PMID: 24490709
Alcohol Preferring (P) Rats; Ethanol; Ondansetron; Topiramate; Combination Treatment
5.  Simulated Driving Performance of Adults with ADHD: Comparisons with Alcohol Intoxication 
Previous research has demonstrated that adults with ADHD are more likely to experience driving-related problems, which suggests that they may exhibit poorer driving performance. However, direct experimental evidence of this hypothesis is limited. The current study involved two experiments that evaluated driving performance in adults with ADHD in terms of the types of driving decrements typically associated with alcohol intoxication. Experiment 1 compared the simulated driving performance of 15 adults with ADHD to 23 adult control participants, who performed the task both while sober and intoxicated. Results showed that sober adults with ADHD exhibited decrements in driving performance compared to sober controls, and that the profile of impairment for the sober ADHD group did in fact resemble that of intoxicated drivers at the BAC level for legally impaired driving in the United States. Driving impairment of the intoxicated individuals was characterized by greater deviation of lane position, faster and more abrupt steering maneuvers, and increased speed variability. Experiment 2 was a dose-challenge study in which 8 adults with ADHD and 8 controls performed the driving simulation task under three doses of alcohol: 0.65 g/kg, 0.45 g/kg, and 0.0 g/kg (placebo). Results showed that driving performance in both groups was impaired in response to alcohol, and that individuals with ADHD exhibited generally poorer driving performance than did controls across all dose conditions. Together the findings provide compelling evidence to suggest that the cognitive and behavioral deficits associated with ADHD might impair driving performance in such a manner as to resemble that of an alcohol intoxicated driver. Moreover, alcohol might impair the performance of drivers with ADHD in an additive fashion that could considerably compromise their driving skill even at blood alcohol concentrations below the legal limit.
PMCID: PMC4305387  PMID: 18540785
6.  Cognitive Deficits Specific to Depression-Prone Smokers During Abstinence 
Cigarette smoking is associated with a higher prevalence of depressive symptoms and individuals with elevated symptoms of depression have more difficulty quitting smoking. Depression is accompanied by cognitive deficits similar to those observed during nicotine withdrawal. Depressed smokers may smoke to alleviate these cognitive symptoms, which are exacerbated upon smoking abstinence. We hypothesized that following overnight abstinence, depression-prone smokers (DP+; past history and current depression symptoms; n = 34) would exhibit deficits in short-term and working memory, and experience greater attentional bias for affective stimuli, compared with smokers with no history or current symptoms of depression (DP−; n = 34). All participants underwent two laboratory sessions, once while smoking abstinent and once while smoking ad libitum (order counterbalanced, abstinence biochemically verified). Smokers completed measures of short-term memory (STM; word recognition task), working memory (N-back task), and attentional bias (Emotional Stroop task). The DP+ group showed declines in STM during abstinence compared with smoking, whereas the DP− group did not (interaction p = .02). There were small decrements in working memory accuracy during abstinence (p = .05), but this did not interact with depression status. During the Emotional Stroop task, the DP+ group showed an attentional bias toward positive versus neutral stimuli during abstinence compared with smoking (interaction p = .01). This study provides initial evidence that depressive symptoms may moderate abstinence-induced deficits in STM and shift attentional bias toward emotionally salient stimuli during abstinence. These cognitive changes may prompt relapse and may help identify novel targets for nicotine dependence treatment aimed at attenuating these deficits to improve cessation rates.
PMCID: PMC4274744  PMID: 24932895
smoking; depression; memory; attentional bias; nicotine withdrawal
7.  Bupropion improves attention but does not affect impulsive behavior in healthy young adults 
Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women) and 11 smokers (4 women) completed four 4-h sessions where they received placebo, bupropion (150 or 300 mg) or d-amphetamine (20 mg) in capsules. Ninety minutes after capsule administration, participants were tested on attention with a Simple Reaction Time Task (SRT) and on impulsivity with the Stop Task, a Delay and Probability Discounting Task (DPD), and the Balloon Analogue Risk Task (BART). Participants also completed mood questionnaires during sessions. Bupropion (150 mg) decreased lapses in attention on the SRT, but did not affect performance on the Stop Task, DPD or BART. d-Amphetamine decreased lapses in attention and speeded sensory motor processing time on the SRT but did not significantly affect responding on the Stop Task or DPD. On the BART, d-amphetamine tended to decrease risk taking in men but increased risk taking in women. Bupropion (300 mg) and d-amphetamine increased ratings of arousal. These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking.
PMCID: PMC4270475  PMID: 18489015
Bupropion; d-Amphetamine; Attention; Smoking Abstinence; Impulsive Behavior; Human
8.  Effects of Nicotine on Attention and Inhibitory Control in Healthy Nonsmokers 
Nicotine improves cognitive functioning in smokers and psychiatric populations, but its cognitive-enhancing effects in healthy nonsmokers are less well understood. Nicotine appears to enhance certain forms of cognition in nonsmokers, but its specificity to subtypes of cognition is not known. This study sought to replicate and extend previous findings on the effects of nicotine on cognitive performance in healthy nonsmokers. Healthy young adults (N=40, 50% female) participated in a placebo-controlled, double-blind, repeated-measures experiment examining the effects of 7mg transdermal nicotine or placebo. Participants completed tests of attention (Attention Network Test), behavioral inhibition (stop signal task, Stroop test), reward responsiveness (signal detection task) and risk-taking behavior (Balloon Analogue Risk Taking task (BART)). Physiological (heart rate, blood pressure) and subjective (Profile of Mood States; POMS, Drug Effects Questionnaire; DEQ) measures were also obtained. Nicotine significantly improved performance only on the Stroop test, but it impaired performance on one aspect of the Attention Network Test, the orienting effect. Nicotine produced its expected effects on physiologic and subjective measures, within the intended time course. The findings of this study contribute to a growing literature indicating that nicotine differentially affects specific subtypes of cognitive performance in healthy nonsmokers.
PMCID: PMC4266322  PMID: 21480731
nicotine; nonsmokers; cognition; attention; inhibitory control
9.  Test-retest reliability of behavioral measures of impulsive choice, impulsive action, and inattention 
Behavioral measures of impulsivity are widely used in substance abuse research, yet relatively little attention has been devoted to establishing their psychometric properties, especially their reliability over repeated administration. The current study examined the test-retest reliability of a battery of standardized behavioral impulsivity tasks, including measures of impulsive choice (delay discounting, probability discounting, and the Balloon Analogue Risk Task), impulsive action (the stop signal task, the go/no-go task, and commission errors on the continuous performance task), and inattention (attention lapses on a simple reaction time task and omission errors on the continuous performance task). Healthy adults (n=128) performed the battery on two separate occasions. Reliability estimates for the individual tasks ranged from moderate to high, with Pearson correlations within the specific impulsivity domains as follows: impulsive choice (r = .76 - .89, ps < .001); impulsive action (r = .65 - .73, ps < .001); and inattention (r = .38-.42, ps < .001). Additionally, the influence of day-to-day fluctuations in mood as measured by the Profile of Mood States was assessed in relation to variability in performance on each of the behavioral tasks. Change in performance on the delay discounting task was significantly associated with change in positive mood and arousal. No other behavioral measures were significantly associated with mood. In sum, the current analysis demonstrates that behavioral measures of impulsivity are reliable measures and thus can be confidently used to assess various facets of impulsivity as intermediate phenotypes for drug abuse.
PMCID: PMC4266373  PMID: 24099351
behavioral impulsivity; impulsive choice; impulsive action; test-retest; reliability
10.  A Pilot Study of Pain-Related Anxiety and Smoking Dependence Motives Among Persons with Chronic Pain 
Complex interactions between pain and tobacco smoking have been of increasing interest to researchers and clinicians from a variety of disciplines. There is also recent evidence to suggest that pain-related anxiety may play an important role in the maintenance of tobacco dependence among persons with comorbid pain disorders. The goal of the current study was to evaluate the explanatory relevance of pain-related anxiety in relation to tobacco dependence, among a sample of daily smokers with current chronic pain. Participants were recruited from the general population to complete an online survey that was developed to examine interrelations between chronic pain and tobacco smoking. Approximately 43% of 129 daily smoking respondents met criteria for current chronic pain. Results indicated that pain-related anxiety accounted for a significant portion of the unique variance in total smoking dependence scores, and both primary and secondary dependence composite scores (as measured by the Wisconsin Inventory of Smoking Dependence Motives). Importantly, these effects were observed above and beyond the variance accounted for by relevant sociodemographic factors, generalized anxiety, and pain severity. Pain-related anxiety was observed to be strongly associated with secondary dependence motives, which is consistent with a conceptualization of pain-related anxiety as an instrumental or situational motivator of smoking. These results suggest that tobacco smokers with comorbid pain disorders may be at risk for maintaining or exacerbating their dependence on tobacco, possibly due to individual differences in pain-related anxiety. These findings may help inform the development of tailored interventions for smokers with comorbid chronic pain.
PMCID: PMC3935323  PMID: 24080021
tobacco; smoking; pain; chronic pain; anxiety; dependence; motives
11.  Attentional Bias for Non-drug Reward is Magnified in Addiction 
Attentional biases for drug-related stimuli play a prominent role in addiction, predicting treatment outcome. Attentional biases also develop for stimuli that have been paired with non-drug reward in adults without a history of addiction, the magnitude of which is predicted by visual working memory capacity and impulsiveness. We tested the hypothesis that addiction is associated with an increased attentional bias for non-drug (monetary) reward relative to that of healthy controls, and that this bias is related to working memory impairments and increased impulsiveness. Seventeen patients receiving methadone maintenance treatment for opioid dependence and seventeen healthy controls participated. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11), visual working memory capacity was measured as the ability to recognize briefly presented color stimuli, and attentional bias was measured as the magnitude of response time slowing caused by irrelevant but previously reward-associated distractors in a visual search task. The results showed that attention was biased toward the distractors across all participants, replicating previous findings. Importantly, this bias was significantly greater in the patients than in the controls and was negatively correlated with visual working memory capacity. Patients were also significantly more impulsive than controls as a group. Our findings demonstrate that patients in treatment for addiction experience greater difficulty ignoring stimuli associated with non-drug reward. This non-specific reward-related bias could mediate the distracting quality of drug-related stimuli previously observed in addiction.
PMCID: PMC3934504  PMID: 24128148
attention; reward; learning; working memory; impulsiveness
12.  Smokers versus snorters: Do treatment outcomes differ according to route of cocaine administration? 
Smoking cocaine achieves maximal concentration and effect far more rapidly than through the intranasal (‘snorting’) route, and it is associated with greater propensity for dependence and more severe consequences. However, very little is known about differences in treatment outcome according to route of administration. This study compared treatment outcomes, such as frequency of cocaine use and Addiction Severity Index (ASI) composite scores, by primary route of cocaine administration (smoking vs. intranasal) among a pooled sample of 412 cocaine-dependent individuals participating in one of five randomized clinical trials. The majority (80%) reported smoking as their primary route of cocaine administration. Overall, results indicated better cocaine use outcomes both during the treatment phase and through a 12-month follow-up period for intranasal users compared to smokers, although not all differences reached statistical significance. Intranasal users remained in treatment longer [F(1,408) = 3.55, p < .05], and showed a trend toward achieving longer periods of sustained abstinence within treatment [F(1,378) = 2.68, p = .08], as well as less use over time during the follow-up period than smokers (Time x Route: t = 1.87, p = .06). Also, intranasal users’ ASI cocaine composite score decreased more than smokers, but there were overall decreases in the other ASI domains for all participants over the course of the study period. These results suggest that intranasal users may achieve better cocaine use outcomes than smokers, yet this doesn't appear to translate to differential changes in the severity of problems experienced in other life areas.
PMCID: PMC3943602  PMID: 24364538
cocaine; route of administration; treatment outcome; problem severity
13.  Impulsivity and Alcohol Demand in relation to Combined Alcohol and Caffeine Use 
Problematic alcohol use among college students continues to be a prominent concern in the United States, including the growing trend of consuming caffeine with alcoholic beverages (CABs). Epidemiologically, CAB use is associated with incremental risks from drinking, although these relationships could be due to common predisposing factors rather than specifically due to CABs. This study investigated the relationship between CAB use, alcohol misuse, and person-level characteristics including impulsive personality traits, delayed reward discounting, and behavioral economic demand for alcohol use. Participants were 273 regularly drinking undergraduate students. Frequency of CAB use was assessed over the past month. A multidimensional assessment of impulsivity included the UPPS-P questionnaire and a validated, questionnaire-based measure of delayed reward discounting. Demand was assessed via a hypothetical alcohol purchase task. Frequency of CAB consumption was significantly higher in males compared to females and was also associated with higher impulsivity on the majority of the UPPS-P subscales, steeper delayed reward discounting, and greater demand for alcohol. Significant correlations between CAB use and both alcohol demand and lack of premeditation remained present after including level of alcohol misuse in partial correlations. In a hierarchical linear regression incorporating demographic, demand, and impulsivity variables, CAB frequency continued to be a significant predictor of hazardous alcohol use. These results suggest that although there are significant associations between CAB consumption and gender, impulsivity, and alcohol demand, CAB use continues to be associated with alcohol misuse after controlling for these variables.
PMCID: PMC4118302  PMID: 24364537
Alcohol; Caffeine; Impulsivity; Demand; Delayed reward discounting
14.  Test-Retest Characteristics of the Balloon Analogue Risk Task (BART) 
The Balloon Analogue Risk Task (BART) is a computerized decision-making task that provides a test of behavioral risk taking. The task is increasingly used in laboratory settings and in the field with young adults and adolescents. However, there are currently no published data about the test-retest characteristics of the task when it is administered on separate days. The current paper addresses this gap. Risky behavior on the BART (adjusted average pumps) showed acceptable test-retest reliability across days (r = +.77, p < .001). The data indicate that risk behavior on the BART has adequate test-retest stability and therefore performance on the task on a single occasion is likely to be representative of an individual’s performance on other occasions.
PMCID: PMC4244869  PMID: 19086777
test-retest validity; test-retest reliability; repeated measures; individual differences; risk behavior
15.  Effects of a Novel CB1 Agonist on Visual Attention in Male Rats: Role of Strategy and Expectancy in Task Accuracy 
The effects of cannabinoid CB1 agonists (including Δ9-tetrahydrocannabinol, the main psychoactive component of marijuana) on attention are uncertain, with reports of impairments, no effects, and occasionally performance enhancements. To better understand these effects, we sought to uncover a role of changing online (within-session) strategy as a possible mediator of the effects of the novel, potent CB1 agonist AM 4054, on a model of sustained attention in male Sprague–Dawley rats. In this operant, two-choice reaction time (RT) task, AM 4054 decreased accuracy in an asymmetric manner; that is, performance was spared on one lever but impaired on the other. Furthermore, this pattern was enhanced by the outcome of the previous trial such that AM 4054 strengthened a win-stay strategy on the “preferred” lever and a lose-shift strategy on the “nonpreferred” lever. This pattern is often found in tests of expectancy; therefore, in a second experiment AM 4054 enhanced expectancy that we engendered by altering the probability of the two stimulus cues. Accuracy was impaired in reporting the less frequent cue, but only after two or more presentations of the more frequent cue. Taking the results of the experiments together, AM 4054 engendered expectancy by increasing the role of previous trial location and outcome on performance of future trials, diminishing stimulus control (and therefore, accuracy). This novel effect of CB1 receptor agonism may contribute to the deleterious effects of cannabinoids on attention.
PMCID: PMC4006576  PMID: 24099361
attention; cannabinoids; decision making; marijuana; operant conditioning
16.  Examining Educational Attainment, Pre-Pregnancy Smoking Rate, and Delay Discounting as Predictors of Spontaneous Quitting Among Pregnant Smokers 
We investigated three potential predictors (educational attainment, pre-pregnancy smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant smokers. These predictors were examined alone and in combination with other potential predictors using study-intake assessments from controlled clinical trials examining the efficacy of financial incentives for smoking cessation and relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118 spontaneous quitters) recruited from the greater Burlington, Vermont area contributed to this secondary analysis, including psychiatric/sociodemographic characteristics, smoking characteristics, and performance on a computerized DD task. Educational attainment, smoking rate, and DD values were each significant predictors of spontaneous quitting in univariate analyses. A model examining those three predictors together retained educational attainment as a main effect and revealed a significant interaction of DD and smoking rate (i.e., DD was a significant predictor at lower but not higher smoking rates). A final model considering all potential predictors included education, the interaction of DD and smoking rate, and five additional predictors (i.e., stress ratings, the belief that smoking during pregnancy will “greatly harm my baby,” age of smoking initiation, marital status, and prior quit attempts during pregnancy. The present study contributes new knowledge on predictors of spontaneous quitting among pregnant smokers with substantive practical implications for reducing smoking during pregnancy.
PMCID: PMC4180793  PMID: 25069014
delay discounting; pregnancy; cigarette smoking; health disparities; spontaneous quitting
17.  Risk-taking and Alcohol Use Disorders Symptomatology in a Sample of Problem Drinkers 
The relationship between risk-taking behavior and alcohol use disorder (AUD) symptoms is poorly understood. This study employed a modified version of a behavioral measure of risk-taking, the Balloon Analogue Risk Task (BART), to examine its relationship to alcohol use and related symptoms in a community sample of individuals with or at risk for AUD. A total of 158 (71.9% male) participants completed a testing battery that included the BART, a structured diagnostic interview for AUD, and measures of alcohol use and related problems. Estimates of IQ and working memory were assessed as covariates. Results indicated that the relationship between risk-taking propensity, as assessed by the BART, and alcohol problems was significant and negative. Individuals with higher symptom count made fewer pumps per trial on the BART, indicating less risk-taking. Importantly, this relationship was attenuated when controlling for estimated IQ and working memory span. Further examination demonstrated that IQ and age mediated the relationship between risk-taking propensity and symptom count. The main negative relationship observed between risk-taking on the BART and alcohol use and AUD symptomatology in this sample stands in contrast to the positive relationships observed in adolescent and non-clinical samples. Together, these findings highlight the need to consider development and the course of addiction in order to fully elucidate the effects of risky-decision making on AUD liability. Furthermore, our results demonstrate the importance of inclusion of neurocognitive covariates (IQ) as well as demographic variables (age) when using this task.
PMCID: PMC4166528  PMID: 21707191
BART; risk-taking; decision-making; impulsivity; alcohol dependence
18.  Methylphenidate does not influence smoking-reinforced responding or attentional performance in adult smokers with and without Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs – the frontline pharmacological treatment for ADHD – influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n=16) and without (n=17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money following oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD.
PMCID: PMC4145471  PMID: 24099358
19.  A Human Alcohol Self-Administration Paradigm to Model Individual Differences in Impaired Control over Alcohol Use 
We developed an alcohol self-administration paradigm to model individual differences in impaired control. The paradigm includes moderate drinking guidelines meant to model limits on alcohol consumption, which are typically exceeded by people with impaired control. Possible payment reductions provided a disincentive for excessive drinking. Alcohol use above the guideline, despite possible pay reductions, was considered to be indicative of impaired control. Heavy-drinking 21–25 year-olds (N = 39) were randomized to an experimental condition including the elements of the impaired control paradigm or to a free-drinking condition without these elements. Alcohol self-administration was compared between these two conditions to establish the internal validity of the experimental paradigm. In both conditions, participants self-administered beer and non-alcoholic beverages for 3 hours in a bar setting with 1–3 other participants. Experimental condition participants self-administered significantly fewer beers and drank to lower blood-alcohol concentrations (BACs) on average than those in the free-drinking condition. Experimental condition participants were more likely than free-drinking condition participants to intersperse non-alcoholic beverages with beer and to drink at a slower pace. Although experimental condition participants drank more moderately than those in the free-drinking condition overall, their range of drinking was considerable (BAC range = .024–.097) with several participants drinking excessively. A lower initial subjective response to alcohol and earlier age of alcohol use onset were associated with greater alcohol self-administration in the experimental condition. Given the variability in response, the impaired control laboratory paradigm may have utility for preliminary tests of novel interventions in future studies and for identifying individual differences in problem-drinking risk.
PMCID: PMC4131292  PMID: 23937598
laboratory methods; young adult; negative consequences; protective strategies; subjective response
20.  A method for conducting functional MRI studies in alert nonhuman primates: initial results with opioid agonists in male cynomolgus monkeys 
Functional magnetic resonance imaging (fMRI) has emerged as a powerful technique for assessing neural effects of psychoactive drugs and other stimuli. Several experimental approaches have been developed to use fMRI in anesthetized and awake animal subjects, each of which has its advantages and complexities. We sought to assess whether one particular method to scan alert post-anesthetized animals can be used to assess fMRI effects of opioid agonists. To date, the use of fMRI as a method to compare pharmacological effects of opioid drugs has been limited. Such studies are important because mu and kappa opioid receptor agonists produce distinct profiles of behavioral effects related both to clinically desirable endpoints (e.g. analgesia) and to undesirable effects (e.g. abuse potential). This study sought to determine whether we could use our fMRI approach to compare acute effects of behaviorally equipotent (3.2 μg/kg) intravenous doses of fentanyl and U69,593 (doses that do not affect cardiorespiratory parameters). Scans were acquired in alert male cynomolgus macaques acclimated to undergo fMRI scans under restraint, absent excessive stress hormone increases. These opioid agonists activated bilateral striatal and nucleus accumbens regions of interest. At the dose tested, U69,593 induced greater left nucleus accumbens BOLD activation than fentanyl, while fentanyl activated left dorsal caudate nucleus more than U69,593. Our results suggest that our fMRI approach could be informative for comparing effects of opioid agonists.
PMCID: PMC3916219  PMID: 23773004
Macaque; fMRI; fentanyl; U69; 593; Awake animal imaging
21.  Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure1 
This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-wk, double blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during week 1, were randomized and inducted onto gabapentin or placebo during week 2, underwent a 10-day buprenorphine taper during weeks 3–4 and then were tapered off gabapentin/placebo during week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male, 17 Caucasian, 3 African American, 4 Latino, mean age 29.7 yrs) participated in the detoxification portion of the study (gabapentin, N=11; placebo, N=13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a drug x time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during weeks 3–4 (OR=0.73, p=0.004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.
PMCID: PMC3972066  PMID: 23855333
Buprenorphine; gabapentin; detoxification; Opioid withdrawal; humans
22.  Initial Development of a Measure of Expectancies for Combinations of Alcohol and Caffeine: The Caffeine+Alcohol Combined Effects Questionnaire (CACEQ) 
Caffeinated alcoholic beverage (CAB) consumption is widespread among young adults in the United States and is associated with increased negative consequences from alcohol. In addition to the direct pharmacological effects of adding caffeine to alcohol, another possible risk mechanism is via socially-learned expectancies, which has received very little consideration. The current study conducted an initial psychometric validation of a measure of CAB expectancies to facilitate research in this area. Participants were 409 undergraduate regular drinkers (71% female) who were assessed for alcohol and CAB use, alcohol use/misuse, and expectancies about CABs. The majority (62%) of participants reported CAB experience and 48% reported CAB use in the past month. Participants primarily consumed spontaneously prepared as opposed to pre-mixed CABs. More frequent CAB use was significantly positively correlated with levels of alcohol use and misuse. For the expectancy items, exploratory factor analysis revealed two factors that were labeled “Intoxication Enhancement” and “Avoid Negative Consequences.” The patterns of expectancies reflected beliefs that CABs enhanced intoxication, but did not protect against negative consequences. The measure was titled the Caffeine+Alcohol Combined Effects Questionnaire (CACEQ). Intoxication enhancement scores were significantly associated with frequency of CAB use, even after adjusting for the role of weekly drinking and alcohol misuse, supporting the convergent validity of the CACEQ. These data provide initial support for the CACEQ and suggest it may be useful for clarifying the role of expectancies in CAB use. Applications for studying the risks associated with CAB use and methodological considerations are discussed.
PMCID: PMC4118292  PMID: 23230858
Alcohol; Caffeine; Caffeinated Alcoholic Beverages; Expectancies; College Drinking
23.  Craving as an Alcohol Use Disorder Symptom in DSM-5: An Empirical Examination in a Treatment-seeking Sample 
Craving has been added as an Alcohol Use Disorder (AUD) symptom in DSM-5 but relatively few nosological studies have directly examined the empirical basis for doing so. The current study investigated the validity of craving as an AUD symptom in a sample of heavy drinking treatment-seeking individuals. Using a semi-structured clinical interview, treatment-seeking heavy drinkers (N = 104; 62% male) were assessed for symptoms of DSM-IV AUD. The extent to which individuals endorsed pathological levels of craving in comparison to other AUD symptoms was investigated as was the association between craving and several aspects of problematic alcohol involvement. Factor analysis was utilized to examine whether craving and other AUD symptoms comprised a unidimensional syndrome. Results indicated that craving was significantly positively correlated with AUD severity, quantitative indices of drinking, and adverse consequences of alcohol abuse. In terms of frequency of endorsement, craving was present in 47% of the sample and was the 8th most frequent of the twelve symptoms evaluated. When considered with the DSM-IV AUD criteria, craving aggregated with other symptoms to form a unidimensional syndrome. Extending previous findings from epidemiological samples, these data suggest that, in a clinical sample, many relevant aspects of craving aggregate to form a diagnostic criterion that functions similarly to other AUD symptoms and is related to diverse aspects of alcohol-related impairment.
PMCID: PMC4105007  PMID: 24490710
Alcohol; Addiction; Craving; Diagnosis; Nosology
24.  Alcohol Expectancies and Reactivity to Alcohol-Related and Affective Cues 
Recent conceptualizations of alcohol expectancies relate cognitive schemas to their neurobiological underpinnings; cue reactivity paradigms lend themselves well to testing this broadened conceptual framework. In the present study, we examined the relationship between self-reported alcohol expectancies and responses to alcohol-related and affective picture cues among fifty-five young adults. In addition to traditional subjective and psychophysiological indices of cue reactivity, the startle eyeblink reflex was obtained during picture cue presentations to address both attention-arousal (early probes) and affective-motivational (late probes) aspects of cue processing. Analyses indicated that participants reporting greater positive, arousing, and social alcohol expectancies rated alcohol cues as more pleasant, arousing, and craving-inducing. In addition, participants displayed inhibited startle reactivity to late alcohol cue probes, indicative of an appetitive reaction. Finally, startle responding to early probes indicated that participants with greater alcohol expectancies displayed blunted attention to negative affect cues. Findings are discussed in terms of the utility of the startle reflex and cue reactivity paradigms for clarifying the relationship between alcohol expectancies and motivated attention to salient cues.
PMCID: PMC4091659  PMID: 19186929
alcohol; cue reactivity; expectancies; startle; affect
25.  Nicotine and Methamphetamine Disrupt Habituation of Sensory Reinforcer Effectiveness in Male Rats 
The reinforcing effectiveness of a sensory stimulus such as light-onset rapidly habituates (Lloyd, Gancarz, Ashrafioun, Kausch, & Richards, 2012). According to memory-based theories, habituation occurs if a memory exists for perceived stimulation, and dishabituation occurs if a memory does not exist and the stimulation is “unexpected.” According to Redgrave and Gurney (2006), unexpected response-contingent sensory stimuli increase phasic firing of dopamine neurons, providing a sensory error signal that reflects the difference between perceived and expected stimuli. Together, memory-based theories of habituation and the sensory error signal hypothesis predict a disruption (slowing) of habituation rate by novel response-contingent sensory stimulation or by artificial increases in dopamine neurotransmission by stimulant drugs. To test these predictions, we examined the effects of stimulant drugs on both the operant level of responding (snout-poking) and operant responding for a sensory reinforcer (light-onset) presented according to a fixed ratio 1 schedule. Robust within-session decreases in responding indicating habituation were observed. The effects of stimulant drugs (saline, n = 10; nicotine, 0.40 mg/kg, n = 10; and methamphetamine, 0.75 mg/kg, n = 9) on habituation in rats were determined. Nicotine was found to decrease habituation rate and did not affect response rate, while methamphetamine decreased habituation rate and increased response rate. In addition, introduction of a novel visual stimulus reinforcer decreased habituation rate and increased responding. These findings show that habituation of reinforcer effectiveness modulates operant responding for sensory reinforcers, and that stimulant drugs may disrupt normally occurring habituation of reinforcer effectiveness by increasing dopamine neurotransmission.
PMCID: PMC4083460  PMID: 24708147
dopamine; operant conditioning; psychomotor stimulants; rats; sensory stimuli

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