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Experimental and Clinical Psychopharmacology - Vol 22, Iss 3

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Experimental & Clinical Psychopharmacology Experimental and Clinical Psychopharmacology seeks to promote the discipline of psychopharmacology in its fullest diversity. Psychopharmacology necessarily involves behavioral change, psychological processes, or their physiological substrates as one central variable and psychopharmacological agents as a second central variable. Such agents will include drugs, medications, and chemicals encountered in the workplace or environment.
Copyright 2014 American Psychological Association
  • Drunk personality: Reports from drinkers and knowledgeable informants.
    Existing literature supports the five-factor model (FFM) of personality (i.e., Extraversion, Agreeableness, Conscientiousness, Emotional Stability, and Intellect or Openness) as a comprehensive representation of stable aspects of mood, affect, and behavior. This study evaluated the FFM as a framework for both self-perceptions of drunkenness (i.e., individual changes in mood, affect, and behavior associated with one’s own intoxication), as well “drinking buddies’” perceptions of their friends’ drunkenness (i.e., changes in mood, affect, and behavior associated with friends’ intoxication) and the association of reported sober-to-drunk differences with negative alcohol-related consequences. College-student drinkers (N = 374; 187 drinking buddy pairs) reported on their sober and drunk levels of the 5 factors, as well as those of their drinking buddies. Buddies completed parallel assessments for themselves and their friends to ensure rater agreement. All participants completed assessments of harmful alcohol outcomes experienced within the past year. Regardless of reporter, differences between drunken and sober states were found across all 5 factors and agreement between self and informant reports was consistently significant and comparable across sober and drunk conditions. Low levels of drunk Conscientiousness and drunk Emotional Stability were associated with experiencing more alcohol-related consequences, even when controlling for sober factor levels and binge-drinking frequency. Findings support the use of the FFM as a clinically relevant framework for organizing differences in personality expression associated with intoxication and the validity of self-reports of drunk personality. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Behavioral economic measures of alcohol reward value as problem severity indicators in college students.
    The aims of the current study were to examine the associations among behavioral economic measures of alcohol value derived from 3 distinct measurement approaches, and to evaluate their respective relations with traditional indicators of alcohol problem severity in college drinkers. Five behavioral economic metrics were derived from hypothetical demand curves that quantify reward value by plotting consumption and expenditures as a function of price, another metric measured proportional behavioral allocation and enjoyment related to alcohol versus other activities, and a final metric measured relative discretionary expenditures on alcohol (RDEA). The sample included 207 heavy-drinking college students (53% female) who were recruited through an on-campus health center or university courses. Factor analysis revealed that the alcohol valuation construct comprises 2 factors: 1 factor that reflects participants’ levels of alcohol price sensitivity (demand persistence), and a second factor that reflects participants’ maximum consumption and monetary and behavioral allocation toward alcohol (amplitude of demand). The demand persistence and behavioral allocation metrics demonstrated the strongest and most consistent multivariate relations with alcohol-related problems, even when controlling for other well-established predictors. The results suggest that behavioral economic indices of reward value show meaningful relations with alcohol problem severity in young adults. Despite the presence of some gender differences, these measures appear to be useful problem indicators for men and women. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • A behavioral economic approach to assessing demand for marijuana.
    In the United States, marijuana is the most commonly used illicit drug. Its prevalence is growing, particularly among young adults. Behavioral economic indices of the relative reinforcing efficacy (RRE) of substances have been used to examine the appeal of licit (e.g., alcohol) and illicit (e.g., heroin) drugs. The present study is the first to use an experimental, simulated purchasing task to examine the RRE of marijuana. Young-adult (M age = 21.64 years) recreational marijuana users (N = 59) completed a computerized marijuana purchasing task designed to generate demand curves and the related RRE indices (e.g., intensity of demand–purchases at lowest price; Omax–max. spent on marijuana; Pmax–price at which marijuana expenditure is max). Participants “purchased” high-grade marijuana across 16 escalating prices that ranged from $0/free to $160/joint. They also provided 2 weeks of real-time, ecological momentary assessment reports on their marijuana use. The purchasing task generated multiple RRE indices. Consistent with research on other substances, the demand for marijuana was inelastic at lower prices but became elastic at higher prices, suggesting that increases in the price of marijuana could lessen its use. In regression analyses, the intensity of demand, Omax, and Pmax, and elasticity each accounted for significant variance in real-time marijuana use. These results provide support for the validity of a simulated marijuana purchasing task to examine marijuana’s reinforcing efficacy. This study highlights the value of applying a behavioral economic framework to young-adult marijuana use and has implications for prevention, treatment, and policies to regulate marijuana use. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • A 5-trial adjusting delay discounting task: Accurate discount rates in less than one minute.
    Individuals who discount delayed rewards at a high rate are more likely to engage in substance abuse, overeating, or problem gambling. Such findings suggest the value of methods to obtain an accurate and fast measurement of discount rate that can be easily deployed in variety of settings. In the present study, we developed and evaluated the 5-trial adjusting delay task, a novel method of obtaining a discount rate in less than 1 min. We hypothesized that discount rates from the 5-trial adjusting delay task would be similar and would correlate with discount rates from a lengthier task we have used previously, and that 4 known effects relating to delay discounting would be replicable with this novel task. To test these hypotheses, the 5-trial adjusting delay task was administered to 111 college students 6 times to obtain discount rates for 6 different commodities, along with a lengthier adjusting amount discounting task. We found that discount rates were similar and correlated between the 5-trial adjusting delay task and the adjusting amount task. Each of the 4 known effects relating to delay discounting was replicated with the 5-trial adjusting delay task to varying degrees. First, discount rates were inversely correlated with amount. Second, discount rates between past and future outcomes were correlated. Third, discount rates were greater for consumable rewards than with money, although we did not control for amount in this comparison. Fourth, discount rates were lower when $0 amounts opposing the chosen time point were explicitly described. Results indicate that the 5-trial adjusting delay task is a viable, rapid method to assess discount rate. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • The role of smoking inflexibility/avoidance in the relation between anxiety sensitivity and tobacco use and beliefs among treatment-seeking smokers.
    Recent scholarly attention has focused on explicating the nature of tobacco use among anxiety-vulnerable smokers. Anxiety sensitivity (fear of aversive internal anxiety states) is a cognitive-affective individual difference factor related to the development and maintenance of anxiety symptoms and disorders and various smoking processes. The present study examined the cross-sectional associations between anxiety sensitivity and a range of cognitive and behavioral smoking processes, and the mediating role of the tendency to respond inflexibly and with avoidance in the presence of smoking-related distress (i.e., avoidance and inflexibility to smoking [AIS]) in such relations. Participants (n = 466) were treatment-seeking daily tobacco smokers recruited as part of a larger tobacco cessation study. Baseline (pretreatment) data were utilized. Self-report measures were used to assess anxiety sensitivity, AIS, and 4 criterion variables: barriers to smoking cessation, quit attempt history, severity of problematic symptoms reported in past quit attempts, and mood-management smoking expectancies. Results indicated that anxiety sensitivity was indirectly related to greater barriers to cessation, greater number of prior quit attempts and greater mood-management smoking expectancies through the tendency to respond inflexibly/avoid to the presence of distressing smoking-related thoughts, feelings, and internal sensations; but not severity of problems experienced while quitting. The present findings suggest AIS may be an explanatory mechanism between anxiety sensitivity and certain smoking processes. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans.
    Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure. Adults with regular cocaine and cigarette use completed this inpatient double blind, randomized, placebo-controlled mixed-design study. A placebo lead-in was followed by randomization to aripiprazole (0, 2 or 10 mg/day/p.o.; n = 7 completed/group). Three sets of test sessions, each consisting of 3 cocaine sample-choice (i.e., self-administration) sessions and 1 dose-response session, were conducted (once during the lead-in and twice after randomization). Sample sessions tested each cocaine dose (0, 20 and 40 mg/70 kg, i.v.) in random order; subjective, observer-rated and physiologic outcomes were collected. Later that day, participants chose between the morning’s sample dose or descending amounts of money over 7 trials. In dose response sessions, all doses were given 1 hr apart in ascending order for pharmacodynamic and pharmacokinetic assessment. Two sets of smoking topography sessions were conducted during the lead-in and after randomization; 1 with and 1 without 40 hr of smoking abstinence. Number of ad lib cigarettes smoked during non-session days was collected. Cocaine produced prototypic effects, but aripiprazole did not significantly alter these effects or smoking outcomes. The smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. These data do not support further investigation of aripiprazole for cocaine or tobacco use disorder treatment. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Cognitive performance in methadone maintenance patients: Effects of time relative to dosing and maintenance dose level.
    Given the long-term nature of methadone maintenance treatment, it is important to assess the extent of cognitive side effects. This study investigated cognitive and psychomotor performance in 51 methadone maintenance patients (MMP) as a function of time since last methadone dose and maintenance dose level. MMP maintained on doses ranging from 40 to 200 mg (mean = 97 mg) completed a battery of psychomotor and cognitive measures across 2 sessions, during peak and trough states, in a double-blind crossover design. Peak sessions were associated with worse performance on measures of sensory processing, psychomotor speed, divided attention, and working memory, compared with trough sessions. The effects of maintenance dose were mixed, with higher dose resulting in worse performance on aspects of attention and working memory, improved performance on executive function, and no effects on several measures. Longer treatment duration was associated with better performance on some measures, but was also associated with increased sensitivity to time since last dose (i.e., worse performance at peak vs. trough) on some measures. The results suggest that cognitive functioning can fluctuate as a function of time since last dose even in MMP who have been maintained on stable doses for an extended time (mean duration in treatment = 4 years), but worsened performance at peak is limited to a subset of functions and may not be clinically significant at these modest levels of behavioral effect. For patients on stable methadone maintenance doses, maintenance at higher doses may not significantly increase the risk of performance impairment. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • The effects of mGluR2/3 activation on acute and repeated amphetamine-induced locomotor activity in differentially reared male rats.
    Environmental stimuli play a key role in affecting the likelihood to abuse drugs. Environmental enrichment can reduce that likelihood. The neurotransmitter glutamate contributes to both drug reward and rearing-induced changes in the brain. The current study investigated the effects of the Group-2 metabotropic glutamate receptor (mGluR2/3) agonist, LY-379268 (0.5, 1.0 mg/kg), on acute and repeated amphetamine-induced locomotor activity in differentially reared male rats. Male Sprague–Dawley rats were randomly assigned to one of 3 environmental conditions postweaning: enriched (EC), isolated (IC), or standard (SC), where they reared for 30 days. The effect of LY-379268 on acute amphetamine-induced locomotor activity was assessed. Rats were injected with either LY-379268 (0.5, 1.0 mg/kg) or saline prior to an amphetamine (0.5 mg/kg) or saline challenge injection. Rats were also administered amphetamine (0.5 mg/kg) or saline injections prior to 5 locomotor sessions. Following a rest period of 14–15 days, the effects of repeated amphetamine exposure were evaluated using LY-379268 (0.5, 1.0 mg/kg) or saline injections 30 min prior to receiving amphetamine (0.5 mg/kg). Results showed that LY-379268 administration dose-dependently attenuated acute amphetamine-induced locomotor activity, with EC rats generally displaying less attenuation than IC or SC rats. After repeated amphetamine administrations, the ability of LY-379268 to attenuate the final expression of amphetamine-induced locomotor activity in differentially reared rats was dose-dependent. The differing effect of LY-379268 observed in EC rats suggests enrichment-induced glutamatergic alterations that may protect against sensitivity to psychostimulants. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Effects of the nicotinic acetylcholine receptor antagonist mecamylamine on the discriminative stimulus effects of cocaine in male rhesus monkeys.
    Preclinical drug discrimination procedures have been useful in understanding the pharmacological mechanisms of the subjective-like effects of abused drugs. Converging lines of evidence from neurochemical and behavioral studies implicate a potential role of nicotinic acetylcholine (nACh) receptors in the abuse-related effects of cocaine. The aim of the present study was to determine the effects of the nACh receptor antagonist mecamylamine on the discriminative stimulus effects of cocaine in nonhuman primates. The effects of mecamylamine on the cocaine-like discriminative stimulus effects of nicotine were also examined. Male rhesus monkeys (n = 5) were trained to discriminate 0.32 mg/kg, IM cocaine from saline in a 2-key, food-reinforced discrimination procedure. Initially, potency and time course of cocaine-like discriminative stimulus effects were determined for nicotine and mecamylamine alone. Test sessions were then conducted examining the effects of mecamylamine on cocaine or the cocaine-like discriminative stimulus effects of nicotine. Curiously, mecamylamine produced partial cocaine-like discriminative stimulus effects. Mecamylamine did not significantly alter the discriminative stimulus effects of cocaine up to doses that significantly decreased rates of operant responding. Mecamylamine and nicotine combinations were not different than saline. These results confirm previous nonhuman primate studies of partial substitution with nicotine and extend these findings with mecamylamine. Furthermore, these results extend previous results in rats suggesting cocaine may have nACh receptor antagonist properties. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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  • Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys.
    d-Amphetamine selectively promotes release of both dopamine (DA) and norepinephrine (NE) versus serotonin (5HT), and chronic d-amphetamine treatment decreases cocaine-taking behavior in rats, nonhuman primates, and humans. However, abuse liability limits the clinical utility of amphetamine maintenance for treating cocaine abuse. One strategy to improve safety and efficacy of monoamine releasers as candidate anticocaine medications has been to develop dual DA/5HT releasers like 1-napthyl-2-aminopropane (PAL-287), but the pharmacology of this class of compounds has not been extensively examined. In particular, PAL-287 has similar potencies to release DA, 5HT, and NE, and the role of manipulating NE release potency on abuse-related or anticocaine effects of dual DA/5HT releasers is not known. To address this issue, the present study compared effects of four novel DA/5HT releasers that varied >800-fold in their selectivities to release DA/5HT versus NE: [1-(5-chloro-1H-indol-3-yl)propan-2-amine (PAL-542), 1-(5-fluoro-1H-indol-3-yl)propan-2-amine (PAL-544), 1-(1H-indol-5-yl)propan-2-amine (PAL-571), and (R)-1-(1H-indol-1-yl)propain-2-amine (PAL-569). Abuse-related effects of all four compounds were evaluated in assays of intracranial self-stimulation (ICSS) in rats and cocaine discrimination in rats and monkeys, and none of the compounds reliably facilitated ICSS or substituted for cocaine. Anticocaine effects of the compound with highest selectivity to release DA/5HT versus NE (PAL-542) were tested in an assay of cocaine versus food choice in rhesus monkeys, and PAL-542 failed to reduce cocaine choice. These results suggests that potency to release NE has minimal influence on abuse liability of dual DA/5HT releasers, and reducing relative potency to release NE versus DA/5HT does not improve anticocaine efficacy. (PsycINFO Database Record (c) 2014 APA, all rights reserved)
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