Justin C. Strickland

Peer Influences on Drug Self-Administration: An Econometric Analysis in Socially Housed Rats

Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs.

Animal models of social contact and drug self-administration

Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self-administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self-administration to guide future research on social learning and drug abuse.

The effects of social contact on drug use: behavioral mechanisms controlling drug intake.

The social environment plays a critical role in determining the likelihood that an individual will use drugs or will develop a drug use disorder. Recent evidence obtained from preclinical studies reveals that proximal social factors (i.e., those factors that are immediately present at the time of drug exposure) exert a particularly strong influence on both drug-seeking and drug-taking behavior. These studies are advancing our understanding of the role of the social environment in drug use by showing that the rewarding and reinforcing effects of drugs depend on (a) whether other individuals are immediately present and (b) whether those individuals are also using drugs. Furthermore, the preclinical literature examining the role of social learning in behavior maintained by nondrug reinforcers reveals a number of behavioral mechanisms by which social contact may influence drug use, as well as potential ways the social environment may be modified to prevent or reduce drug use. Additional research is needed to determine potential age and sex differences in the effects of social contact on drug use, to determine the generality of the current findings across different pharmacological classes of drugs, and to determine the role of social contact on drug intake during different transitional stages of drug use disorders; however, enough evidence now exists to begin implementing social interventions in clinical and at-risk populations.

Perceptions of research risk and undue influence: Implications for ethics of research conducted with cocaine users

BACKGROUND Despite the prominence of human laboratory and clinical trial research in the development of interventions for substance use disorders, this research presents numerous ethical challenges. Ethical principles outlined in the Belmont Report, including respect for persons, beneficence, and justice, have traditionally guided research conduct. Few empirical studies exist examining substance abuse research ethics. The present study examined perceptions of beneficence and respect for persons in substance use research, including relative risk and desired monetary compensation, using an online sample of cocaine users. METHODS The study was conducted on Amazon.coms Mechanical Turk (mTurk), a crowdsourcing website used for survey-based research. Of 1764 individuals screened, 138 reported past year cocaine use. These respondents completed a battery of standardized and experimenter-designed questionnaires used to characterize each respondents self-reported attitudes, beliefs, and behaviors about drug use and the relative risks and desired monetary compensation associated with research participation. RESULTS Ratings of relative risk revealed that most respondents found common research practices as less than or equal to the relative risk of everyday life. Receiving experimental medication outside the hospital was rated as the most risky research activity, but on average was not rated as presenting more risk than everyday life. Desired compensation for research participation was associated with the perceived risk of research activities. Increases in desired compensation for participation were only observed for research perceived as much more risky than everyday activities. CONCLUSIONS These findings indicate that cocaine users assess risk in a way that is consistent with standard research practice.

Animal models of resistance exercise and their application to neuroscience research.

BACKGROUND Numerous studies have demonstrated that participation in regular resistance exercise (e.g., strength training) is associated with improvements in mental health, memory, and cognition. However, less is known about the neurobiological mechanisms mediating these effects. The goal of this mini-review is to describe and evaluate the available animal models of resistance exercise that may prove useful for examining CNS activity. NEW METHOD Various models have been developed to examine resistance exercise in laboratory animals. COMPARISON WITH EXISTING METHODS Resistance exercise models vary in how the resistance manipulation is applied, either through direct stimulation of the muscle (e.g., in situ models) or through behavior maintained by operant contingencies (e.g., whole organism models). Each model presents distinct advantages and disadvantages for examining central nervous system (CNS) activity, and consideration of these attributes is essential for the future investigation of underlying neurobiological substrates. RESULTS Potential neurobiological mechanisms mediating the effects of resistance exercise on pain, anxiety, memory, and drug use have been efficiently and effectively investigated using resistance exercise models that minimize stress and maximize the relative contribution of resistance over aerobic factors. CONCLUSIONS Whole organism resistance exercise models that (1) limit the use of potentially stressful stimuli and (2) minimize the contribution of aerobic factors will be critical for examining resistance exercise and CNS function.

Differential sensitivity to learning from positive and negative outcomes in cocaine users.

BACKGROUND Altered sensitivity to positive and negative outcomes may be linked to the maladaptive choices characteristic of substance use disorders. Few studies have determined the distinct roles that positive and negative outcomes play in stimulus-response learning in cocaine users. The purpose of the present study was to investigate sensitivity to learning from positive and negative outcomes on a probabilistic learning task in cocaine users employing human laboratory and crowdsourcing techniques. METHODS Individuals who reported cocaine use were recruited for a laboratory study (Experiment 1) or an online study on Amazon.coms Mechanical Turk (mTurk) (Experiment 2). All participants completed a feedback-based probabilistic learning task in which images were classified into categories (A versus B). Positive and negative outcomes were provided in a probabilistic manner on separate trials. Proportion of optimal responses and response times were recorded. RESULTS Active cocaine users were less sensitive to learning from positive relative to negative outcomes. These effects were consistent across image type and session in the laboratory sample. Similarly, reduced sensitivity to learning from positive outcomes was observed in cocaine users on mTurk. Control participants did not show suboptimal performance following positive or negative outcomes. CONCLUSIONS This study extends the limited research on feedback-based learning in drug users by demonstrating reduced sensitivity to positive outcomes in cocaine users recruited in the human laboratory and online. Future studies on the clinical significance and mechanisms underlying this bias are needed to understand its relevance as a target for intervention development.

The effects of social contact on cocaine intake under extended-access conditions in male rats.

Social learning theories of drug use propose that drug use is influenced by the behavior of peers. We previously reported that cocaine self-administration under limited-access conditions can be either facilitated or inhibited by social contact, depending on the behavior of a peer. The purpose of this study was to determine whether social contact influences cocaine self-administration under conditions that are more representative of problematic patterns of drug use. Male rats were assigned to either isolated or pair-housed conditions in which a social partner either had access to cocaine or did not have access to cocaine. Pair-housed rats were tested in custom-built operant conditioning chambers that allowed both rats to be tested simultaneously in the same chamber. In Experiment 1, rats were tested for 14 consecutive days during daily 6-hr test sessions. In Experiment 2, different doses of cocaine were tested in 23-hr test sessions conducted every 3 days. All groups of rats escalated their cocaine intake in Experiment 1; however, pair-housed rats with a partner without access to cocaine had lower levels of intake throughout the 14 days of testing. In Experiment 2, pair-housed rats with a partner without access to cocaine had lower levels of cocaine intake than did rats with a partner with access to cocaine, and this effect was observed at all doses of cocaine tested. These data indicate that the behavior of a social partner (i.e., whether or not that partner is also self-administering cocaine) influences cocaine self-administration under conditions that model problematic patterns of drug use. (PsycINFO Database Record

Mu opioid mediated discriminative-stimulus effects of tramadol: an individual subjects analysis.

Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human participants. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human participants first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to participants after they acquired the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all participants. These effects were attenuated by naltrexone. Individual participant records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure.

The effects of a shared history of drug exposure on social choice.

Selection theories of drug use propose that individuals choose or self-select into peer groups on the basis of perceived similarities with other group members with regard to their beliefs, attitudes, and histories of drug use. The purpose of the present study was to determine whether a shared history of drug exposure would influence choice of a social partner. Adolescent male rats were treated with either cocaine (3.0 mg/kg, intraperitoneally) or saline and their preference for a cocaine-treated rat or a saline-treated rat was measured in a partner preference test. Next, a series of conditioning trials were conducted in which rats were paired with a cocaine-treated and a saline-treated partner on alternating days for 10 days. Finally, a second partner preference test was conducted, in which preference for cocaine-treated and saline-treated partners was reassessed. Relative to baseline, rats showed an increase in the amount of time they spent with their similarly treated partner, and this effect was driven by cocaine-treated rats increasing the amount of time spent in proximity to their cocaine-treated partner after conditioning. These findings support a selection model of drug use by showing that a shared history of drug exposure is sufficient to establish a social preference for one individual over another.

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users

Cocaine users display deficits in inhibitory control and make impulsive choices that may increase risky behavior. Buspirone is an anxiolytic that activates dopaminergic and serotonergic systems and improves impulsive choice (i.e., reduces sexual risk‐taking intent) in cocaine users when administered chronically. We evaluated the effects of acutely administered buspirone on inhibitory control and impulsive choice.