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Experimental and Clinical Psychopharmacology - Vol 23, Iss 4

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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 2015 American Psychological Association
  • Sex differences in drug abuse: Etiology, prevention, and treatment.
    This special issue exemplifies one of the major goals of the current editor of Experimental and Clinical Psychopharmacology (Dr. Suzette Evans): to increase the number of manuscripts that emphasize females and address sex differences. Taken together, these articles represent a broad range of drug classes and approaches spanning preclinical research to treatment to better understand the role of sex differences in drug abuse. While not all studies found sex differences, we want to emphasize that finding no sex difference is just as important as confirming one, and should be reported in peer-reviewed journals. It is our intention and hope that this special issue will further advance scientific awareness about the importance of accounting for sex differences in the study of substance abuse. Participant sex is an essential variable to consider in developing a more comprehensive understanding of substance abuse. Rather than viewing investigating sex differences as burdensome, investigators should seize this opportune area ripe for innovative research that is long overdue. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex differences in monoamines following amphetamine and social reward in adolescent rats.
    Interaction with social peers may increase rates of drug self-administration, but a recent study from our laboratory showed that social interaction may serve as a type of alternative reward that competes with drug taking in adolescent male rats. Based on those previous results, the current study examined sex differences in preference for social interaction compared with amphetamine (AMPH) in adolescent rats using the conditioned place preference (CPP) paradigm. Similar to previous results with males, females showed AMPH CPP regardless of whether they were individual- or pair-housed. In contrast to males, however, females failed to show social CPP, and they did not prefer a peer-associated compartment over an AMPH-associated compartment in a free-choice test. In separate experiments, dopamine (DA) and serotonin (5-HT) metabolite levels were measured in adolescent males and females that were exposed acutely to peer interaction, no peer interaction, AMPH, or saline. In amygdala, levels of the DA metabolite dihydroxyphenylacetic acid (DOPAC) were altered more in response to peer interaction in males than females; in contrast, there was a greater amygdala DOPAC response to AMPH in females. Furthermore, there were greater changes in the 5-HT metabolite hydroxyindoleacetic acid (5-HIAA) in females than in males following social interaction. These results indicate that the ability of peer interactions to reduce drug reward is greater in adolescent males than females, perhaps due to a greater ability of social cues to activate limbic reward mechanisms in males or a greater ability of AMPH cues to activate limbic reward mechanisms in females. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • The impact of gonadal hormones on cannabinoid dependence.
    Cannabis is the most widely used illicit substance in the United States. Women report greater positive subjective effects of cannabis, and greater cannabis withdrawal compared to men. Female rodents are more sensitive than males to some acute effects of Δ⁹-tetrahydrocannabinol (THC), and females also develop greater tolerance to THC in some assays. The purpose of this study was to determine whether gonadal hormones modulate THC dependence in rats. Adult rats were gonadectomized (GDX) or sham-GDX, and hormone was replaced in half of the GDX rats of each sex (testosterone in males; estradiol and/or progesterone in females). THC (30 mg/kg) or vehicle was administered twice daily for 6.5 days, followed on the seventh day by vehicle or rimonabant challenge and assessment for withdrawal-related behaviors. Sham-GDX females developed greater tolerance than males to THC-induced hypothermia, and GDX females given progesterone showed greater tolerance to THC-induced locomotor suppression. Rimonabant precipitated withdrawal, as evidenced by increased somatic signs (forepaw tremors, licking) and increased startle amplitude. Testosterone in GDX males decreased withdrawal-induced licking. Estradiol and progesterone in GDX females increased withdrawal-induced chewing, and progesterone increased withdrawal-induced sniffing. These results suggest that estradiol and progesterone may promote the development of dependence, whereas testosterone may protect against dependence. While the present study indicates that testosterone and estradiol produce opposite effects on THC-induced behavior, estradiol appears to play a broader role than testosterone in modulating THC’s behavioral effects. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Discriminative stimulus effects of morphine and oxycodone in the absence and presence of acetic acid in male and female C57Bl/6 mice.
    The use of prescription opioids for clinical management of pain remains problematic because of concerns about addiction associated with opioid use. Another difficulty in pain management is the increasing evidence for sex differences in pain behavior and opioid-induced behavioral effects. However, few studies have documented the abuse potential of prescription opioids as a function of pain in rodents, with significant gaps in the literature pertaining to sex differences in the interaction between pain and opioid effects. The present study evaluated the effects of an experimentally induced acute pain state (acetic acid injections) on the potency of morphine and oxycodone to produce discriminative stimulus effects in male and female C57Bl/6 mice trained to discriminate 3.2 mg/kg morphine from saline. Acetic acid injections attenuated the stimulus potency of morphine by 2.2-fold but not the stimulus potency of oxycodone in male mice. Acetic acid injections did not alter the discriminative stimulus effects of either morphine or oxycodone in female mice. The antinociceptive effects of the 2 opioids were evaluated using the acetic acid–induced stretching test. For antinociceptive effects, morphine was 2.0-fold less potent relative to oxycodone in male mice, whereas morphine and oxycodone were equipotent in female mice. Taken together, these results indicate that acetic acid–induced acute pain differentially modulates the discriminative stimulus effects of morphine in male and female mice and that this change may be related to the variable antinociceptive effectiveness of these opioids across sexes. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Effects of consuming a diet high in fat and/or sugar on the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice.
    Drug abuse and obesity are serious public health problems. Dopamine plays a central role in mediating the reinforcing effects of drugs and food. Prolonged use of drugs is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine; however, the impact of consuming foods high in fat and/or sugar is less clear. These studies characterized the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice consuming 1 of 4 diets: (a) standard chow + water; (b) standard chow + 10% sucrose solution; (c) high-fat chow + water; or (d) high-fat chow + 10% sucrose solution. The acute locomotor effects of cocaine (3.2–32.0 mg/kg) were evaluated 4 weeks after initiating dietary conditions; the effects of repeated cocaine administration were evaluated after 5, 6, 7, and 12 weeks. During acute tests, mice consuming a diet high in fat and/or sucrose exhibited greater locomotor responses to cocaine than mice consuming standard chow and water, regardless of sex. Although diet-induced enhancements persisted across repeated cocaine testing, locomotor sensitization developed more rapidly in females drinking sucrose (and consuming either standard or high-fat chow) than in females consuming standard chow and water. In addition to providing evidence that consuming a diet high in fat and/or sugar enhances abuse-related effects of cocaine in ways that might increase vulnerability to abuse cocaine, these studies identified a potentially important sex-related difference in the interaction between nutrition and cocaine effects, with the impacts of sucrose consumption being greater in females than in males. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.
    Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex differences in resting state brain function of cigarette smokers and links to nicotine dependence.
    Sex—a marker of biological and social individual differences—matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and nonsmokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, the authors demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional MRI and behavioral data from 50 adult daily smokers (23 women), the authors found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Speech volume indexes sex differences in the social-emotional effects of alcohol.
    Men and women differ dramatically in their rates of alcohol use disorder (AUD), and researchers have long been interested in identifying mechanisms underlying male vulnerability to problem drinking. Surveys suggest that social processes underlie sex differences in drinking patterns, with men reporting greater social enhancement from alcohol than women, and all-male social drinking contexts being associated with particularly high rates of hazardous drinking. But experimental evidence for sex differences in social-emotional response to alcohol has heretofore been lacking. Research using larger sample sizes, a social context, and more sensitive measures of alcohol’s rewarding effects may be necessary to better understand sex differences in the etiology of AUD. This study explored the acute effects of alcohol during social exchange on speech volume—an objective measure of social-emotional experience that was reliably captured at the group level. Social drinkers (360 male; 360 female) consumed alcohol (.82 g/kg males; .74 g/kg females), placebo, or a no-alcohol control beverage in groups of 3 over 36-min. Within each of the 3 beverage conditions, equal numbers of groups consisted of all males, all females, 2 females and 1 male, and 1 female and 2 males. Speech volume was monitored continuously throughout the drink period, and group volume emerged as a robust correlate of self-report and facial indexes of social reward. Notably, alcohol-related increases in group volume were observed selectively in all-male groups but not in groups containing any females. Results point to social enhancement as a promising direction for research exploring factors underlying sex differences in problem drinking. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex differences in self-report and behavioral measures of disinhibition predicting marijuana use across adolescence.
    Disinhibition has been consistently linked to substance use across development. Recent research suggests, however, that these relations may be influenced by both sex and measurement approach. The current study examined the moderating effect of sex on the association between behavioral and self-report measures of disinhibition and marijuana use across adolescence. Participants were 115 boys and 89 girls initially evaluated at Grade 8 using a laboratory behavioral assessment and self-report questionnaires of disinhibitory variables. Marijuana use was measured annually from Grades 9 through 12. Results suggest that boys and girls did not differ on either self-reported or behaviorally assessed levels of disinhibition, and that disinhibition measured using both approaches was associated with increases in marijuana use over time. There was a significant interaction between sex and disinhibition, suggesting that boys (but not girls) who self-reported elevations in disinhibition evidenced greater increases in marijuana use. The current findings add to a growing literature supporting the importance of using multiple methods to assess disinhibition and highlight the critical role of biological sex in understanding these relations. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Effects of sex composition on group processes in alcohol prevention groups for teens.
    Although most alcohol and other drug prevention programs for adolescents are offered in group settings, little is known about the possible effects of sex composition on group processes and mechanisms of change. Using the Group Actor–Partner Interdependence Model framework, we examined how the sex constellation of adolescent prevention group members influenced youth satisfaction, engagement, and endorsement of healthy behavior during group. Participants in Project Options (N = 379; 61.8% girls; Mage = 16.1; SD = 1.4), a voluntary school-based alcohol prevention program, completed measures of satisfaction at each prevention session and observers rated engagement and change talk for each group. When analyses were oriented toward girls, their personal satisfaction, group-rated satisfaction, and group-level engagement were positively related to having more girls in the group. Similarly, in boys, personal satisfaction, satisfaction of the group as a whole, and engagement in groups improved when groups were composed of more girls. Statements supportive of healthy alcohol/drug-related decision making were unrelated to group composition. The findings suggest that the composition of girls and boys in groups has differential effects on some group processes. This avenue of research has merit for understanding the mechanisms associated with satisfaction and engagement in adolescent substance use prevention programs. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex effects in cocaine-using methadone patients randomized to contingency management interventions.
    Contingency management (CM) is an effective treatment for promoting cocaine abstinence in patients receiving methadone maintenance. However, few studies have examined the effect of sex on treatment outcomes in this population. This study evaluated the impact of sex on longest duration of abstinence (LDA) and percent negative urine samples in 323 cocaine-using methadone patients from 4 randomized clinical trials comparing CM to standard methadone care. Overall, women had better treatment outcomes compared with men, demonstrated by an increase in both LDA and percentages of negative samples. Patients receiving CM also had significantly higher LDA and percentages of negative samples compared to patients receiving standard care, but sex by treatment condition effects were not significant. These data suggest that cocaine-using methadone patients who are women have better substance use outcomes than men in interventions that regularly monitor cocaine use, and CM is equally efficacious regardless of sex. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sex differences in the latent class structure of alcohol use disorder: Does (dis)aggregation of indicators matter?
    Many researchers have argued for a differential presentation of alcohol use disorder (AUD) between men and women. Latent class analysis is the most commonly used analytic technique for modeling AUD subcategories, and latent class analyses have supported a variety of class structures of AUD. This article examines whether these differential results are, in part, an artifact of whether researchers have (a) analyzed men and women in the same analysis and (b) aggregated item-level symptoms into AUD diagnostic criteria prior to analysis. These related methodological issues are examined using Wave 2 data from the National Epidemiologic Survey of Alcohol and Related Conditions (N = 22,177). Direct comparison of results when the sexes are modeled separately or together shows that women are classified differently depending on whether men are included in the analysis. A comparison of disaggregated item-level symptoms and aggregated AUD criteria suggests that aggregating data remove a subgroup, individuals who exhibit tolerance but are normative on all other AUD symptoms, which is of theoretical and clinical interest. Consequently, basic methodological issues that are rarely systematically studied appear to be important determinants of studies seeking to determine whether male and female alcoholism are structurally isomorphic. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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