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1.  Not so bad: avoidance and aversive discounting modulate threat appraisal in anterior cingulate and medial prefrontal cortex 
The dorsal anterior cingulate (adACC) and dorsal medial prefrontal cortex (dmPFC) play a central role in the discrimination and appraisal of threatening stimuli. Yet, little is known about what specific features of threatening situations recruit these regions and how avoidance may modulate appraisal and activation through prevention of aversive events. In this investigation, 30 healthy adults underwent functional neuroimaging while completing an avoidance task in which responses to an Avoidable CS+ threat prevented delivery of an aversive stimulus, but not to an Unavoidable CS+ threat. Extinction testing was also completed where CSs were presented without aversive stimulus delivery and an opportunity to avoid. The Avoidable CS+ relative to the Unavoidable CS+ was associated with reductions in ratings of negative valence, fear, and US expectancy and activation. Greater regional activation was consistently observed to the Unavoidable CS+ during avoidance, which declined during extinction. Individuals exhibiting greater aversive discounting—that is, those more avoidant of immediate monetary loss compared to a larger delayed loss—also displayed greater activation to the Unavoidable CS+, highlighting aversive discounting as a significant individual difference variable. These are the first results linking adACC/dmPFC reactivity to avoidance-based reductions of aversive events and modulation of activation by individual differences in aversive discounting.
PMCID: PMC4461832  PMID: 26113813
avoidance; threat; fear; anterior cingulate; medial prefrontal cortex; loss discounting; anxiety; neuroimaging
2.  Combined Diffraction and Density Functional Theory Calculations of Halogen-Bonded Cocrystal Monolayers 
Langmuir  2013;29(48):14903-14911.
This work describes the combined use of synchrotron X-ray diffraction and density functional theory (DFT) calculations to understand the cocrystal formation or phase separation in 2D monolayers capable of halogen bonding. The solid monolayer structure of 1,4-diiodobenzene (DIB) has been determined by X-ray synchrotron diffraction. The mixing behavior of DIB with 4,4′-bipyridyl (BPY) has also been studied and interestingly is found to phase-separate rather than form a cocrystal, as observed in the bulk. DFT calculations are used to establish the underlying origin of this interesting behavior. The DFT calculations are demonstrated to agree well with the recently proposed monolayer structure for the cocrystal of BPY and 1,4-diiodotetrafluorobenzene (DITFB) (the perfluorinated analogue of DIB), where halogen bonding has also been identified by diffraction. Here we have calculated an estimate of the halogen bond strength by DFT calculations for the DITFB/BPY cocrystal monolayer, which is found to be ∼20 kJ/mol. Computationally, we find that the nonfluorinated DIB and BPY are not expected to form a halogen-bonded cocrystal in a 2D layer; for this pair of species, phase separation of the components is calculated to be lower energy, in good agreement with the diffraction results.
PMCID: PMC3968856  PMID: 24215390
3.  Effects of Acute Pramipexole on Preference for Gambling-like Schedules of Reinforcement in Rats 
Psychopharmacology  2010;213(1):11-18.
Pramipexole and other direct dopamine agonist medications have been implicated in the development of impulsive behavior such as pathological gambling among those taking the drug to control symptoms of Parkinson’s disease or restless leg syndrome. Few laboratory studies examining pramipexole’s effects on gambling-like behavior have been conducted.
The present study used a rodent model approximating some aspects of human gambling to examine within-subject effects of acute pramipexole (0.03, 0.1, 0.18, & 0.3 mg/kg) on rat’s choices to earn food reinforcement by completing variable-ratio (i.e., gambling-like) or fixed-ratio response requirements.
In a condition in which the variable-ratio alternative was rarely selected, all but the lowest dose of pramipexole significantly increased choice of the variable-ratio alternative (an average of 15% above saline).. The same doses did not affect choice significantly in a control condition designed to evaluate the involvement of nonspecific drug effects. Pramipexole increased latencies to initiate trials (+ 9.12 s) and to begin response runs on forced-choice trials (variable-ratio: + 0.21 s; fixed-ratio: + 0.88 s), but did not affect measures of response perseveration (conditional probabilities of “staying”).
The findings are consistent with clinical reports linking pramipexole to the expression of increased gambling in humans. Results are discussed in the context of neurobehavioral evidence suggesting that dopamine agonists increase sensitivity to reward delay and disrupt appropriate feedback from negative outcomes.
PMCID: PMC3747984  PMID: 20814781
pramipexole; dopamine agonist; gambling; impulsive behavior; Parkinson’s disease; rat
In recent years, researchers and practitioners in the behavioral sciences have profited from a growing literature on delay discounting. The purpose of this article is to provide readers with a brief tutorial on how to use Microsoft Office Excel 2010 and Excel for Mac 2011 to analyze discounting data to yield parameters for both the hyperbolic discounting model and area under the curve. This tutorial is intended to encourage the quantitative analysis of behavior in both research and applied settings by readers with relatively little formal training in nonlinear regression.
PMCID: PMC3405931  PMID: 22844143
behavioral economics; delay discounting; impulsivity; Microsoft Excel; technology
5.  Delay Discounting in Lewis and Fischer 344 Rats: Steady-state and Rapid-determination Adjusting-amount Procedures 
Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.
PMCID: PMC3372954  PMID: 22693360
Lewis rats; Fischer 344 rats; delay discounting; adjusting amount; impulsive choice; lever press; rat
6.  Delay Discounting and Gambling 
Behavioural processes  2011;87(1):43-49.
Delay discounting describes the decline in the value of a reinforcer as the delay to that reinforcer increases. A review of the available studies revealed that steep delay discounting is positively correlated with problem or pathological gambling. One hypothesis regarding this correlation derives from the discounting equation proposed by Mazur (1989). According to the equation, steeper discounting renders the difference between fixed-delayed rewards and gambling-like variable-delayed rewards larger; with the latter being more valuable. The present study was designed to test this prediction by first assessing rats’ impulsive choices across four delays to a larger-later reinforcer. A second condition quantified strength of preference for mixed- over fixed-delays, with the duration of the latter adjusted between sessions to achieve indifference. Strength of preference for the mixed-delay alternative is given by the fixed delay at indifference (lower fixed-delay values reflect stronger preferences). Percent impulsive choice was not correlated with the value of the fixed delay at indifference and, therefore, the prediction of the hyperbolic model of gambling was not supported. A follow-up assessment revealed a significant decrease in impulsive choice after the second condition. This shift in impulsive choice could underlie the failure to observe the predicted correlation between impulsive choice and degree of preference for mixed- over fixed delays.
PMCID: PMC3081402  PMID: 21352902
Delay discounting; impulsivity; delay; gambling; rat
7.  Effects of Pramipexole on Impulsive Choice in Male Wistar Rats 
Clinical reports, primarily with Parkinson’s patients, note an association between the prescribed use of pramipexole (and other direct-acting dopamine agonist medications) and impulse control disorders, particularly pathological gambling. Two experiments examined the effects of acute pramipexole on rats’ impulsive choices where impulsivity was defined as selecting a smaller-sooner over a larger-later food reward. In Experiment 1, pramipexole (0.1 to 0.3 mg/kg) significantly increased impulsive choices in a condition in which few impulsive choices were made during a stable baseline. In a control condition, in which impulsive choices predominated during baseline, pramipexole did not significantly change the same rats’ choices. Experiment 2 explored a wider range of doses (0.01 to 0.3 mg/kg) using a choice procedure in which delays to the larger-later reinforcer delivery increased across trial blocks within each session. At the doses used in Experiment 1, pramipexole shifted choice toward indifference regardless of the operative delay. At lower doses of pramipexole (0.01 & 0.03 mg/kg), a trend toward more impulsive choice was observed at the 0.03 mg/kg dose. The difference in outcomes across experiments may be due to the more complex discriminations required in Experiment 2; i.e., multiple discriminations between changing delays within each session.
PMCID: PMC3021944  PMID: 20545391
Pramipexole; D2/D3 agonist; Impulsivity; Choice; Gambling
Previous research has shown that Lewis rats make more impulsive choices than Fischer 344 rats. Such strain-related differences in choice are important as they may provide an avenue for exploring genetic and neurochemical contributions to impulsive choice. The present systematic replication was designed to determine if these findings could be reproduced using a procedure less susceptible to within- or between-session carry-over effects that may have affected previous findings. Specifically, delays to the larger–later food reinforcer were manipulated between conditions following steady-state assessments of choice, and the order of delays across conditions was mixed. The results confirmed previous findings that Lewis rats made significantly more impulsive choices than Fischer 344 rats. Fischer 344 rats' preference for the larger–later reinforcer, on the other hand, was less extreme than reported in prior research, which may be due to carry-over effects inherent to the commonly used technique of systematically increasing delays within session. Previously reported across-strain motor differences were reproduced as Lewis rats had shorter latencies than Fischer 344 rats, although these latencies were not correlated with impulsive choice. Parallels between reduced dopamine function in Lewis rats and clinical reports of impulse-control disorders following treatment of Parkinson patients with selective D2/D3 dopamine agonists are discussed.
PMCID: PMC2582207  PMID: 19070340
Fischer 344 rats; Lewis rats; choice; impulsivity; delay-discounting; rat; lever press

Results 1-8 (8)