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BACKGROUND: An important factor that can lead to drug relapse is to re-associate with drug-using social peers, but there is little literature on the effect of social peers on relapse in animal models. METHODS: The current study used a dual-compartment operant conditioning apparatus that allowed adult male rats to respond for cocaine in the presence of a conspecific. In Experiment 1, rats were trained to self-administer cocaine in the presence of a social peer that was separated by a wire screen partition and then that peer was used as a reinstatement cue following a period of extinction. In the next experiments, rats were trained on alternating sessions to self-administer cocaine in the presence of one peer and to self-administer saline in the presence of a different peer using either a single active lever procedure (Experiment 2) or a double active lever procedure (Experiment 3). Following extinction of responding in the absence of the peers, the effect of re-exposure to the cocaine- and saline-associated peers on reinstatement of drug seeking was determined. This was tested using both single- and double-active lever procedures. RESULTS: In Experiment 1, a peer that was present throughout cocaine self-administration was able to reinstate cocaine seeking following a period of extinction. In Experiments 2 and 3, drug seeking was reinstated by the cocaine-associated peer (S+), but not the saline-associated peer (S-). This discrimination occurred when using either the single active lever procedure or double active lever procedure. CONCLUSION: These results indicate that a social peer can be used as a discriminative stimulus to signal cocaine availability and that re-introduction of a peer previously paired with cocaine can reinstate cocaine seeking, confirming clinical reports that peer affiliation among abstinent cocaine users is an important determinant of relapse.

Adolescence is a period associated with increased risk taking and peer relations. Research has shown that age is correlated with vulnerability to peer pressure, with youth being more influenced by peers compared with adults, leading to exacerbated risk taking, including risk for drug abuse. Preclinical research suggests that these findings may also be applicable to rodents, as younger rats find social interaction rewarding and are prone to risky behavior. However, there is little research on the effect of social interaction on rodent models of risky decision making. This study examined risky decision making utilizing a dual-compartment apparatus that consisted of two adjacent operant conditioning chambers separated by a wire mesh screen partition that allowed for limited social interaction. Male rats performed a risky decision making task in which they had a choice between a small reinforcer and larger reinforcer that was associated with a mild footshock, which increased in probability across the session. Rats were initially trained during adolescence and performance on the task was assessed in the presence or absence of a peer in the adjacent chamber during young adulthood. Results revealed that there was less risk discounting, leading to greater preference for the larger, risky reinforcer, in rats that had daily exposure to a social peer during training. These results provide evidence that social influence on risk taking can be modeled in rats, perhaps having implications for drug abuse risk. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Negative urgency is a facet of impulsivity that is known to be associated with problematic substance use, as well as a host of other health-related negative outcomes. The urgency, premediation (lack of), perseverance (lack of), sensation seeking (UPPS) scale is used to measure negative urgency in humans. Recent evidence indicates that high and low negative urgency subjects respond differently on a reward omission task using monetary incentives. Following omission of an expected reward, high-urgency subjects are more frustrated and display greater impulsive responding compared to low-urgency subjects. This task has also been used in rats to investigate the neurobiology of negative urgency. Converging evidence now indicates that a neural system involving interconnections between the prefrontal cortex and amygdala may play a key role in individual differences in negative urgency. This work may inform prevention scientists and practitioners implementing drug abuse prevention and treatment interventions.

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.

Cocaine use is associated with high levels of impulsive choice (greater discounting of delayed rewards) in humans, but the cause/effect relationships between cocaine use and impulsive choice are not fully understood. In previous work, we found that both experimenter- and self-administration of fixed quantities of cocaine caused lasting increases in impulsive choice in rats. The present study extended these findings by taking into account baseline impulsive choice prior to self-administration, and by allowing rats free access to cocaine. Male Long-Evans rats were trained in a delay discounting task in which they made discrete-trial choices between small immediate and large delayed food rewards. Half of the rats were then implanted with intravenous catheters and, following recovery, allowed to self-administer cocaine HCl (1.0 mg/kg/infusion) in 6 hour sessions over 14 days. Control rats orally self-administered a sucrose solution under similar conditions. Upon completion of self-administration training, rats remained abstinent for 3 weeks before retesting in the delay discounting task. Cocaine and control groups did not differ prior to self-administration, but afterward, the cocaine group showed greater impulsive choice (fewer choices of large, delayed rewards) than controls. Additional analyses revealed that the effects of cocaine on impulsive choice were intake-dependent; rats classified as “low intake” did not differ from controls, whereas rats classified as “high intake” were significantly more impulsive than both controls and their pre-cocaine baseline. These findings are consistent with the idea that cocaine-induced, pharmacologically based neural adaptations promote the development of impulsive decision making.

Poor decision making and elevated risk taking, particularly during adolescence, have been strongly linked to drug use; however the causal relationships among these factors are not well understood. To address these relationships, a rat model (the Risky Decision-making Task; RDT) was used to determine whether individual differences in risk taking during adolescence predict later propensity for cocaine self-administration and/or whether cocaine self-administration causes alterations in risk taking. In addition, the RDT was used to determine how risk taking is modulated by dopamine signaling, particularly in the striatum. Results from these experiments indicated that greater risk taking during adolescence predicted greater intake of cocaine during acquisition of self-administration in adulthood, and that adult cocaine self-administration in turn caused elevated risk taking that was present following 6 weeks of abstinence. Greater adolescent risk taking was associated with lower striatal D2 receptor mRNA expression, and pharmacological activation of D2/3 receptors in the ventral, but not dorsal, striatum induced a decrease in risk taking. These findings indicate that the relationship between elevated risk taking and cocaine self-administration is bi-directional, and that low striatal D2 receptor expression may represent a predisposing factor for both maladaptive decision making and cocaine use. Furthermore, these findings suggest that striatal D2 receptors represent a therapeutic target for attenuating maladaptive decision making when choices include risk of adverse consequences.

Drug and Alcohol Dependence 156 (2015) e183–e245 e237 However, a small subgroup of participants exhibited a worsening course, characterizedby the initiationofheroinuseand/or injection opioid use. Financial support: NIDA grants U10 DA15831. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.637 Sex differences in dopamine and serotonin activation of brain pathways in adolescent rats exposed to social partners or amphetamine Virginia G. Weiss1,∗, Rebecca S. Hofford1, Justin R. Yates2, Michael T. Bardo1 1 University of Kentucky, Lexington, KY, United States 2 Northern Kentucky University, Newport, KY, United

Aims: Attention-Deficit/Hyperactivity Disorder (ADHD) is an independent risk factor for cigarette smoking. Although smokers withADHDdiffer fromnon-ADHDsmokers inmany respects, ADHD is a heterogeneous disorder composed of different subtypes. Given that past research has demonstrated differences between ADHD subtypes, including studies examining nicotine dependence, the aim of the current studywas to assess ADHD subtype differences in the immediate consequences of smoking using ecological momentary assessment (EMA). In particular, we aimed to assess subtype differences in smoking to regulate affect and ADHD symptoms. Methods: Smokers with ADHD (n=17) were subdivided into ADHD Predominately Inattentive (n=9) and ADHD Combined (n=8) subtypes followingadiagnostic assessment. Participants carried an electronic diary for at least 7 days and provided entries for each cigarette they smoked. Results: Both groups did not differ in nicotine dependence severity. 1232 EMA smoking entries were recorded. Participants responded to questions immediately prior to and after each cigarette. The ADHD Combined subtype reported significantly greater reductions in boredom (p= .011), total ADHD symptoms (p= .019), inattentive ADHD symptoms (p= .013), and hyperactiveimpulsive ADHD symptoms (p= .048) than the ADHD Inattentive subtype in a series of ANOVA’s. In addition, the Combined subtype reported a statistically significant improvement in positive affect after smoking (p= .038). Subtypes did not differ in smoking to regulate urge to smoke, negative affect, anxiety, stress, hunger, worry, or general restlessness. Conclusions: These findings have implications for the role of affect and ADHD symptom regulation in smoking maintenance among ADHD subtypes. Particularly, thosewith the Combined subtype may smoke to regulate ADHD symptoms, positive affect, and negative affect, whereas those with the Inattentive subtype may smoke to regulate primarily negative affect. Financial support: This research was supported by Grant R03DA029694 (John T. Mitchell).