Heavy drinking has increased in recent years and has been linked to numerous health-related risks, particularly in women. A number of factors may play a role in exacerbating the risks linked to heavy drinking, such as impulsivity, which itself is related to a number of risky behaviors. The present study investigated the effects of alcohol (0, 0.5, 0.75 g/kg) on impulsivity in female heavy drinkers (n = 23) and female light drinkers (n = 23) using a double-blind, placebo-controlled outpatient design; all women were tested during follicular phase of the menstrual cycle. Each session, participants completed a range of tasks including subjective measures of abuse liability, cognitive performance tasks, three behavioral impulsivity tasks, and a risk-taking task. Alcohol increased impulsivity on the Immediate and Delayed Memory Task (IMT and DMT) and Delay Discounting task. Heavy drinkers scored higher on impulsivity self-reports and were more impulsive on the IMT and the GoStop task than light drinkers. The high dose of alcohol further increased impulsive performance on the IMT and DMT in heavy drinkers. There were no group differences or alcohol effects on the Balloon Analogue Risk Task. Alcohol increased sedative-like effects more in light drinkers and increased stimulant-like effects and alcohol liking more in heavy drinkers. In summary, female heavy drinkers are less sensitive to the negative effects of alcohol, report more positive effects of alcohol, and are more impulsive than female light drinkers. Moreover, impulsive responding was exacerbated by alcohol drinking among female heavy drinkers, indicating that women who drink at this level are at increased risk for developing alcohol use disorders and engaging in other risky behaviors, particularly after drinking.
impulsivity; alcohol; abuse liability; heavy drinking; women
Understanding sensory reinforcement and the effects of stimulant drugs on sensory reinforcers is potentially important for understanding their influence on addiction processes. Experiment 1 explored the reinforcing properties of a visual stimulus and the effects of methamphetamine (METH) on responding maintained by a visual reinforcer (VRF) in male rats. Snout poke responses to the active alternative produced the VRF according to variable interval (VI) schedules of reinforcement, and responses to an inactive alternative had no programmed effect. Experiment 2 explored the effects of METH on choice between the VRF and a water reinforcer (H2ORF) using concurrent VI schedules in male rats. In Experiment 1, response-contingent onset of the VRF produced an increase in both the relative frequency and absolute rate of active responding. The rate of both active and inactive responding declined across the 40-min test sessions. METH did not differentially enhance active responding for the VRF. Instead, METH nondifferentially increased the rate of responding and attenuated the within-session decline of responding. In Experiment 2, METH differentially increased the rate of responding for the VRF relative to the H2ORF. The results of these exploratory experiments indicate that the reinforcing effects of the VRF were weak and transient. In addition, METH treatment increased responding, and the specificity of the enhancement of METH was dependent upon the testing conditions. Potential explanations of these differences, such as novelty and reinforcer type, are discussed.
novelty; drug abuse; operant conditioning; rats; learning
Nonmedical use of prescription stimulant medication such as methylphenidate (MPH) has increased among college students over the past several years. Common motivations for use include enhancements in cognition and subjective arousal. As it is unclear whether stimulant medication exerts the same effect on healthy individuals as for those with ADHD, it is possible that many reported effects of prescription stimulants by healthy individuals may stem from placebo effects, which may be an important mechanism underlying initiation and maintenance of nonmedical use. This study examined whether placebo effects influence reports of subjective mood and cognitive performance among college students who endorsed several risk factors for prescription stimulant misuse (i.e., low GPA, fraternity/sorority involvement, binge drinking, cannabis use). Ninety-six subjects (60% male) completed a battery of cognitive tests and questionnaires assessing present mood state on two occasions. Forty-seven participants were randomized to an experimental condition and orally ingested what they believed to be MPH, though actually placebo, on one visit and received no medication on the other visit. The control group received no medication on either visit. During the administration visit, experimental participants reported feeling significantly more high and stimulated compared to the non-administration visit and to the control subjects. However, cognitive enhancement differences were not generally seen between visits or groups. This research demonstrates that placebo effects for prescription stimulants do influence subjective mood and may be implicated in nonmedical stimulant use. This knowledge may be useful in challenging prescription stimulant-related expectancies to decrease the prevalence of use among college students.
prescription stimulants; placebo effects; expectancy effects; cognition; college students
The dopamine D3 receptor has received attention over the last two decades as a target for medications development for substance abuse disorders. Results have remained mixed. Despite emergence of more D3-selective ligands, possible attribution of observed effects to D2 receptors remains a concern. Knockout mice may help shed light on mechanisms. Here we evaluated the effect of constitutive D3 receptor inactivation (“knockout”) on the reinforcing effects of cocaine. We tested D3 wild-type (WT), heterozygous (D3+/−), and knockout (D3−/−), mice in acquisition and maintenance of intravenous self-administration across a broad range of cocaine doses, using a fixed ratio (FR) 1 and a progressive ratio (PR) schedule of reinforcement, along with parallel food-reinforced studies. Generally, D3−/− mice showed cocaine self-administration comparable to WT controls across assays. Moderate and nonsignificant trends toward lesser reinforcing effects of a low cocaine dose (0.32 mg/kg) were apparent in acquisition and PR studies, consistent with the idea that the D3 receptor may play a subtle role in the reinforcing effects of low cocaine doses under low FR conditions. However, those effects with cocaine self-administration were more subtle than the lower responding of D3 knockout mice observed with food-maintained behavior. In addition, the D3 antagonist PG01037 failed to affect cocaine self-administration under an FR 1 schedule in WT mice. The present data do not support a necessary role for the D3 receptor in the direct reinforcing effects of cocaine.
cocaine; dopamine receptors; knockout mice; progressive ratio; food-maintained behavior
Cigarette cravings in response to environmental cues and stressors are widely recognized as important predictors of smoking cessation outcomes. Accumulating evidence suggests that genetics plays a role in these craving responses, as well as in smoking cessation more generally. Previous studies of genetic polymorphisms have been limited by examination of single candidate genes and the use of broadly defined phenotypes (e.g., smoking history). In addition, research examining the similarities and differences between cue- and stress-induced cravings has been limited, although some evidence has suggested that they may have common genetic underpinnings. In the current study, we examined associations between a panel of 1,350 candidate genetic polymorphisms and craving responses to laboratory smoking cues and stressors. We hypothesized that common genetic polymorphisms would be predictive of both cue- and stress-induced craving. Nicotine-dependent smokers (n = 210) donated a blood sample, were exposed to neutral, smoking-related, and stress-related stimuli, and completed craving questionnaires immediately prior to and following each stimulus. Findings indicated that craving responses to smoking cues and stressors were moderately correlated (r = .44). However, genetic analysis revealed that cue and stress-induced cigarette craving were predicted by different polymorphisms, such that variants in the glycine and dopamine pathways were predictive of cue-induced craving, whereas variants in the stress-corticotropin pathway predicted stress-induced craving. Conclusions: Study results provide no support for the hypothesis that cue- and stress-induced craving have the same genetic predictors.
smoking; stress; cue; craving; genetic factors
Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval.
chlordiazepoxide; pentobarbital; cocaine; d-amphetamine; rate-dependent; reinforcement magnitude; fixed-interval; pigeon; rat
This study aimed to identify correlates of smoking cessation failure, a failure to establish abstinence during a quit smoking attempt. Identifying risk factors for early failure could facilitate the development of tailored interventions to promote cessation. The current study used existing ecological momentary assessment (EMA) data to investigate the extent to which pre-quit craving, negative affect, and recent smoking were associated with cessation failure in 374 smokers (189, 50.5% female). Subjects were prompted to complete 4–7 real-time reports of craving, negative affect, and recent smoking daily in the four days prior to quitting. Multilevel models of craving and negative affect (mean level, growth, volatility, and association with smoking) were estimated. Results indicated that recent smoking was associated with significantly lower craving among smokers who failed to quit than those who achieved a full day of cessation, but this held only among smokers who reduced smoking by at least 10% in the days preceding the quit attempt. Smokers who failed to quit on the quit day also experienced slower increases in negative affect in the days preceding the quit attempt than did initial abstainers, but delayed quitters and delayed cessation failures did not differ in negative affect trajectories. These results suggest that successful abstainers and cessation failures can be differentiated by specific dimensions of pre-quit craving and negative affect experiences, but the effects hold only in certain circumstances.
Craving; Ecological Momentary Assessment; Smoking Cessation
Age at the time of first alcohol and cannabis use was investigated in relation to a measure of transmissible (intergenerational) risk for addiction in childhood and development of alcohol use disorder (AUD) and cannabis use disorder (CUD). It was hypothesized that age at the time of first experience with either substance mediates the association between transmissible risk and subsequent diagnosis of both disorders. The Transmissible Liability Index (TLI; (Vanyukov et al., 2009) was administered to 339 10- to 12-year-old boys (n = 254) and girls (n = 85). Age at the time of first alcohol and cannabis use, and diagnosis of AUD and CUD, were prospectively tracked to age 22. Each standard deviation unit increase in TLI severity corresponded to a reduction in age of alcohol and cannabis use onset by 3.2 months and 4.6 months, respectively. Age at the time of first alcohol use mediated the association of TLI with both AUD and CUD. Parallel results were obtained for cannabis. Whereas transmissible risk is congenerous to both AUD and CUD, its magnitude was 7 times greater in youths who initiated substance use with cannabis. TLI predicts age of first use of alcohol and cannabis that is common to developing both AUD and CUD. The ramifications of these findings for prevention are discussed.
substance use disorder; transmissible risk; cannabis; alcohol; childhood
The extended-release formulation of zolpidem (Ambien CR®) is approved for the treatment of insomnia without a treatment duration limit. Acutely zolpidem impairs performance, and no research to date has examined whether tolerance develops to these performance impairments during nighttime awakening. The present double-blind, placebo-controlled study examined whether tolerance develops to zolpidem-induced acute performance impairment after repeated (22–30 days) nightly use. Effects of bedtime administration of zolpidem extended-release (ZOL; 12.5 mg) were tested on a battery of performance measures assessed during a forced nighttime awakening in 15 healthy male volunteers who completed overnight polysomnographic recording sessions in our laboratory at baseline and after approximately a month of at-home ZOL. As expected, bedtime ZOL administration was associated with changes in sleep architecture and impairments across all performance domains during nighttime testing (psychomotor function, attention, working memory, episodic memory, metacognition) with no residual next morning impairment. Tolerance did not develop to the observed ZOL-related impairments on any outcome. Possible evidence of acute abstinence effects following discontinuation of ZOL was observed on some performance and sleep outcomes. Overall, these findings suggest that performance is significantly impaired during nighttime awakening even after a month of nightly ZOL administration and these impairments could significantly impact safety should nighttime awakening require unimpaired functioning (e.g., driving; combat-related activities in the military).
zolpidem; Ambien; psychomotor; cognition; tolerance; memory
Women account for a quarter of all new HIV/AIDS cases, with approximately 65% having contracted the infection via heterosexual contact (CDC, 2008). Few experimental studies have examined interactions among background, partner, and situational characteristics in predicting women’s sexual decisions. The Cognitive Mediation Model provides a useful theoretical framework for assessing likelihood of unprotected sex (Norris, Masters, & Zawacki, 2004). Female social drinkers (n = 230) who had answered questions related to their general intention to have unprotected sex were randomly assigned to an experimental condition based on partner risk level (unknown, low, high) and beverage (control, placebo, low dose, high dose). Participants projected themselves into a story depicting a sexual situation with a man and answered questions about their cognitive appraisals, assertive condom request, and likelihood of unprotected sex. Alcohol effects on appraisal of sexual potential differed by partner risk condition. In the unknown and low risk conditions, placebo and alcohol participants appraised the situation as having greater sexual potential than controls whereas in the high risk condition, only those who consumed alcohol did so. Sexual potential appraisals in turn predicted impelling cognitions about having sex, which in turn predicted assertive condom request and unprotected sex intentions. General intention for unprotected sex independently predicted cognitive appraisals and outcomes. These findings highlight the need for prevention programs that focus on teaching women how to pay attention and consider sexual risk cues presented by potential partners, particularly when under the influence of alcohol.
alcohol consumption; partner risk; condom use; condom request; risky sex
Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions.
The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of i.v. nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to i.v. cocaine (another short-acting stimulant) were also studied.
Fourteen (1 female) volunteers participated in this 3-4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudorandomized order, in which oral caffeine (250 mg/70kg) or placebo was administered 1 h before an i.v. injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline.
Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of “rush,” “good effects,” “liking,” “high,” and “drowsy/sleepy.” Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine.
In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects.
nicotine; caffeine; cocaine; human; blood pressure
The subjective experience of nicotine, which may be influenced by personality traits as well as environmental factors, may be important for understanding the factors associated with the initiation and maintenance of nicotine dependence. The present study examined the effects of 7 mg transdermal nicotine among a relatively large sample (n=91; 44 female) of college-aged nonsmokers. Using a placebo controlled, double-blind, within-subjects design, nicotine’s effects were examined at rest and again after participants completed a sustained attention task. Sex and personality factors (Behavioral Inhibition and Behavioral Approach; BIS/BAS) were examined as potential moderators. Overall, the effects of nicotine were generally modest and unpleasant. In the context of the cognitive task, nicotine increased nausea and negative affect but reduced fatigue, relative to placebo. In contrast, effects of nicotine during the initial 4 hours of patch administration, in which participants were in their natural environments, were moderated by individual differences in behavioral approach. Neither behavioral inhibition nor gender reliably moderated any subjective effects of nicotine. The present work suggests transdermal nicotine exerts only modest, mostly negative effects among nonsmokers. Future work should examine both contextual and personality moderators in large samples of participants who are exposed to nicotine through multiple routes of administration.
subjective effects; transdermal nicotine; nonsmokers; affect; smoking
Individual vulnerability to psychopathologies is linked to a number of genetic polymorphisms including the serotonin transporter (5HTT) promoter polymorphic region (5HTTLPR). A single copy of the short variant (s-variant) allele of 5HTTLPR confers increased susceptibility to anxiety disorders and depression and decreased efficacy of serotonin-releasing agents in pharmacotherapy compared to the homozygous long 5HTTLPR variant (l/l). The data suggesting that the 5HTTLPR polymorphism modulates the efficacy of serotonin-releasing agents in pharmacotherapy is inconsistent. Other factors such as age, gender, and hormonal status could interact with 5HTTLPR genotype to affect individual physiological and behavioral responses to serotonin reuptake inhibitors such as citalopram. Indeed, estradiol and progesterone, the primary female steroid hormones, exert an array of effects on the serotonergic system, including 5HTT expression. The present study used ovariectomized female rhesus monkeys to determine the interaction between the 5HTTLPR polymorphism and the effects of mid-follicular levels of estradiol and luteal levels of progesterone on serotonergic responsivity to acute citalopram administration. The increase in serum prolactin, a surrogate measure of serotonin activity, following citalopram administration was significantly larger in l/l females than in s-variant females over the course of two hours during concurrent estradiol and progesterone hormone replacement only. These data suggest that ovarian function and the 5HTTLPR polymorphism interact to gate serotonergic reactivity in females, suggesting that clinicians should be aware of the ovarian status and 5HTTLPR genotype of women when considering serotonergic pharmacotherapy in women.
serotonin transporter; citalopram; estradiol; progesterone; females
Contingency management (CM) treatments that provide patients with the opportunity to earn chances of winning prizes of varying magnitudes are becoming increasingly popular. In the CM literature, magnitude of reinforcement is linked with effect sizes, such that CM treatments that provide larger magnitude reinforcement are more efficacious than those that provide lower magnitude reinforcement. With prize CM, even when magnitudes of overall expected prize earnings are constant, some patients win more prizes than others. Thus, patients who win larger overall amounts of prizes during treatment may have better outcomes than those who win fewer prizes. This study evaluated the impact of overall amounts of prizes won on long-term abstinence outcomes. The dollar amount of prizes won during prize CM treatments was determined from 78 cocaine abusing methadone maintenance patients who were randomized to prize CM treatments in three clinical trials. Abstinence three months following the end of the CM intervention was the primary dependent variable. The dollar amount of prizes won during CM treatment was a significant predictor of submission of cocaine-negative urine samples and self reports of cocaine abstinence at the follow-up evaluation, even after controlling for other variables associated with long-term abstinence such as pre-treatment urinalysis results and longest duration of abstinence achieved during treatment. These results suggest that magnitudes of earnings during prize CM may impact outcomes and call for further experimentation of parameters related to the efficacy of prize CM.
contingency management; methadone maintenance; cocaine
Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders.
In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients.
Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values.
DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week (t(33) = 2.48, p = .045) and entire recommended 24-week of treatment (t(33) = 2.40, p = .022). Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = −1.12, p = .271; 24-week: t(32) = −0.37, p = .712).
These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response.
Temporal discounting; delay discounting; cocaine dependence; contingency management; vouchers; treatment response
Relative to intravenous drug self-administration, locomotor activity is easier to measure with high throughput, particularly in mice. Therefore its potential to predict differences in self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) is appealing, but such predictive value is unverified. The main goal of this study was to evaluate the utility of the locomotor assay for accurately predicting differences in cocaine self-administration. A second goal was to evaluate any correlation between activity in a novel environment, and cocaine-induced hyperactivity, between strains. We evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but BALB/cJ mice showed locomotor habituation and significant cocaine-induced hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine self-administration. As previously reported, female rats showed greater cocaine-induced locomotion than males, but this was only observed in one of fifteen mouse strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ, BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some correlation between all-or-none locomotion in a novel environment, and stimulant and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced activity offered a clear prediction of relative reinforcing effects among strains. Additionally, these results should aid in selecting mouse strains for future studies in which relative locomotor responsiveness to psychostimulants is a necessary consideration.
cocaine; locomotor activity; self-administration; BALB/cJ; BALB/cByJ
Many neurological and psychiatric disorders are treated with dopamine modulators. Studies in mice may reveal genetic factors underlying those disorders or responsiveness to various treatments, and species and strain differences both complicate the use of mice and provide valuable tools. We evaluated psychomotor effects of the dopamine D1-like agonist R-6-Br-APB and the dopamine D2-like agonist quinelorane using a locomotor activity procedure in 15 mouse strains (inbred 129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, outbred Swiss Webster and CD-1) and Sprague Dawley rats, using groups of both females and males. Both D1 and D2 stimulation produced hyperactivity in the rats, and surprisingly, only two mouse strains were similar in that regard (C3H/HeJ, SPRET/EiJ). In contrast, the majority of mouse strains exhibited hyperactivity only with D1 stimulation, whereas D2 stimulation had no effect or decreased activity. BALB substrains, A/J and FVB/NJ mice showed only decreased activity following either D1 or D2 stimulation. CAST/EiJ mice exhibited hyperactivity exclusively with D2 stimulation. Sex differences were observed but no systematic trend emerged: For example, of the five strains in which a main factor of sex was identified for the stimulant effects of the D1 agonist, responsiveness was greatest in females in three of those strains and in males in two of those strains. These results should aid in the selection of mouse strains for future studies in which D1 or D2 responsiveness is a necessary consideration in the experimental design.
quinelorane; R-6-Br-APB; mouse strains; locomotor activity; direct dopamine agonists
Based on evidence suggesting that depressive traits, emotional information processing, and the effects of nicotine may be mediated by lateralized brain mechanisms, analyses assessed the influence of depressive traits and nicotine patch on emotional priming of lateralized emotional word identification in 61 habitual smokers. Consistent with hypotheses, nicotine as compared to placebo patch enhanced right visual field (RVF) emotional word identification while decreasing performance of emotional word identification in the left visual field (LVF). Nicotine also enhanced positive affect and decreased negative affect. Consistent with the Heller model of depression, scoring high in depressive traits was associated with a general decrease in LVF emotional word identification. Additionally, this general LVF deficit was especially pronounced for positive word identification in individuals scoring high in trait depression. Positive primes facilitated positive target identification in the RVF and negative primes facilitated negative target identification in the LVF. Thus, nicotine promoted a LVF word-identification deficit similar to that observed in those with depressive traits. However, nicotine also enhanced RVF processing and reduced negative affect, while it enhanced positive affect.
depression; nicotine; emotion; cerebral asymmetry; affect; priming
The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on i.v. methamphetamine self-administration (1 - 30 µg/kg/injection) in rhesus monkeys. When given as a pre-session i.m. injection, a high dose of methamphetamine (1.0 mg/kg) decreased i.v. methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of i.m. methamphetamine required to reduce i.v. methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.
Methamphetamine; self-administration; bupropion; methylphenidate; rhesus monkeys
We used multimodal measurement to evaluate whether (a) nicotine dependence is associated with baseline and postquit negative affect and craving, (b) smoking relapse is associated with greater negative affect and craving than abstinence, and (c) craving is associated with negative affect. Treatment-seeking smokers were randomly assigned to either a brief behaviorally based smoking-cessation treatment condition or to a delayed treatment control condition. Participants in the treatment condition attended four assessment sessions, 4 –5 days prequit (baseline), 1–2 days postquit, 3–5 days postquit, and 10 –14 days postquit, while controls attended four sessions spaced over the same intervals. Retrospective questionnaires were collected at the beginning of each session, and corrugator EMG and in-session ratings were collected during viewing of affective and cigarette-related slides. The multimodal measures indicated that more dependent smokers experienced greater negative affect and craving at baseline and postquit, regardless of abstinence status. The self-report measures indicated that both relapsed and abstinent smokers reported greater negative affect and craving than control smokers. Craving was associated with negative affect across measurement modalities. These results highlight the benefits of using multimodal measures to study the impact of nicotine dependence and withdrawal on negative affect and craving.
smoking cessation; withdrawal; negative affect; craving; corrugator EMG
Much effort has been devoted to examining the differences in postcessation affective experience between smoking abstainers and relapsers. However, little attention has been given to the affective changes of smokers who, despite their motivation to quit, fail to achieve even a brief period of abstinence. Using affect-modulated startle response and self-report questionnaires, we measured the postcessation affective changes of 115 smokers (60 men, 55 women) who participated in a laboratory investigation of affective reactivity during smoking cessation. Among our participants, 34 were abstainers (16 men, 18 women), 16 were never-quitters (8 men, 8 women), 19 were relapsers (8 men, 11 women), and 46 were controls (28 men, 18 women). We found a significant Stimulus Valence × Session × Group interaction effect on startle responses, which suggested that while abstainers, relapsers, and control exhibited the prototypical affect-modulated startle response across postcessation sessions, never-quitters displayed an atypical response pattern in which emotional pictures no longer modulated the startle response. Never-quitters also reported increasingly higher negative and lower positive affect across postcessation sessions. Using affect-modulated startle response and self-report questionnaires, this study found a significant difference in the affective reactivity between smokers who could and smokers who could not establish an initial abstinence of 24 hours.
smoking; affect-modulated startle responses; nicotine withdrawal; negative affect; smoking relapse
This report describes a novel procedure for computer-controlled drug-dose determination for IV drug self-administration studies. By modifying the duration of each infusion of a single concentration of a drug solution, five or more unit doses (mg/kg/inj) can be dispensed from the same syringe. The advantages of this procedure include the following: (1) it is not necessary to prepare a new syringe for each dose change; (2) the sterility of the IV catheter line is broken less often and; (3) the confounding effect of flushing through the catheter line with the previous drug dose is avoided. This procedure is accurate and reliable and can be applied to multiple sessions of any duration across days or weeks.
Drug self-administration; Computer-controlled drug doses; Drug dose-effect curves
Individuals with attention deficit hyperactivity disorder (ADHD) smoke at rates significantly higher than the general population and have more difficulty quitting than nondiagnosed individuals. Currently, there are no evidence-based approaches for reducing smoking specifically in individuals with ADHD. Adult regular smokers with or without ADHD participated in a study of extended smoking withdrawal where monetary incentives were used to promote abstinence. Participants were paid according to an escalating schedule for maintaining abstinence measured as self-report of no smoking and an expired air carbon monoxide (CO) level of ≤4 parts per million. Sixty-four percent (14/22) of smokers with ADHD and 50% (11/22) of smokers without ADHD maintained complete abstinence for the 2-week duration of the study. Twenty-two percent (5/22) and 9% (2/22) of smokers with ADHD and without ADHD, respectively, maintained continued abstinence for up to 10 days following the removal of the contingencies. Though abstinence rates were higher for the smokers with ADHD, the group differences were not statistically significant. Results suggest that monetary incentives may be a useful approach for promoting abstinence in adult smokers with ADHD, perhaps owing to altered reinforcement processes in these individuals.
ADHD; smoking; nicotine dependence; contingency management
Chronic cocaine users are known to have cognitive deficits that are predictive of poor treatment response. Whether these deficits improve with medications targeting specific cognitive functions has not been examined in previous studies. The goal of this study was to evaluate galantamine’s efficacy on selected cognitive outcomes, including measures of sustained attention, response inhibition, and attentional bias in recently abstinent cocaine users. Galantamine, a reversible and competitive inhibitor of acetylcholinesterase, is used clinically in the treatment of Alzheimer’s dementia. In a randomized, double-blind, parallel-group study, 34 participants were randomized to galantamine (8 mg/day) or placebo treatment for 10 days. Cognitive and self-report mood measures were obtained at baseline and on days 5 and 10 after the initiation of treatment. Galantamine treatment, compared to placebo, improved the reaction time, F(2,50)=8.6, p <0.01, detection sensitivity (A′), F(2,50)=4.9, p <0.03, number of hits, F(2,50)=4.2, p <0.04, and number of correct rejections, F(2,50)=5.6, p <0.02, on the Rapid Visual Information Processing (RVIP) task. With the exception of speeding the reaction time on the Stroop, galantamine did not affect performance on other tasks, (p>0.05). These results demonstrate that medications can enhance cognitive function (e.g. sustained attention) in abstinent cocaine users. The potential efficacy of galantamine as a treatment for cocaine abuse needs to be further evaluated in clinical trials.
Galantamine; cholinesterase inhibitor; cocaine; cognitive function
Misuse of prescription opioid medications has continued as a major public health problem in the United States. Review of major epidemiologic data bases shows that the prevalence of opioid misuse rose markedly through the 1990’s and the early part of the current decade. In this same period of time the number of prescriptions for chronic non-cancer pain increased markedly, and the intersection of these two public health problems remains a concern. Further, despite some leveling off of the overall rate of prescription opioid misuse in the past several years, surveillance data show high and increasing mortality associated with these drugs. Analysis of the 2006 National Survey of Drug Use and Health indicates the increasing prevalence of prescription opioid misuse is associated more with an increase in the general availability of these medications than misuse of the medications by those who were directly prescribed them. National Institute on Drug Abuse initiatives to address the prescription opioid problem include programs to stimulate research in the basic and clinical sciences, and education of physicians and other health personnel.
prescription opioid misuse; drug addiction; chronic pain; prevalence of opioid abuse; NIDA National Institute on Drug Abuse