Rationale Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed. Objectives The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol. Methods Outbred CFW mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.5 min), or moderate (30 bites: mean = 3.8 min) stress. Plasma corticosterone was measured on days 1 and 10 of the defeat. Ethanol drinking during continuous access to alcohol was measured 10 days following the defeat or 10 days prior to, during and 20 days after the defeat. Motivation to drink was determined using a PR operant conditioning schedule during intermittent access to ethanol. Results Plasma corticosterone was elevated in both stress groups on days 1 and 10. Ethanol consumption and preference following moderate social stress was higher than both the mild stress group and controls. Mice with previously acquired ethanol drinking showed decreased ethanol consumption during the moderate stress followed by an increase 20 days post-defeat. Moderately stressed mice also showed escalated ethanol intake (11g/kg/day) and ethanol self-administration during a schedule of intermittent access to alcohol. Conclusion Social defeat experiences of moderate intensity and duration led to increased ethanol drinking and preference in CFW mice. Ongoing work investigates the interaction between glucocorticoids and dopaminergic systems as neural mechanisms for stress-escalated alcohol consumption.

In addition to its classical role in mediating responses to pain, the opioid system is strongly implicated in the regulation of social behavior. In young laboratory animals, low doses of opioid analgesic drugs reduce responses to isolation distress and increase play behavior. However, little is known about how opioid drugs affect responses to social stimuli in humans. Here we examined the effects of buprenorphine, a mu-opioid partial agonist and kappa-antagonist, on three dimensions of social processing; i) responses to simulated social rejection, ii) attention to emotional facial expressions, and iii) emotional responses to images with and without social content. Healthy adults (N = 36) attended two sessions during which they received either placebo or 0.2mg sublingual buprenorphine in randomized order, under double-blind conditions. Ninety minutes after drug administration, they completed three behavioral tasks: i) a virtual ball-toss game in which they were first included and then excluded by the other players; ii) an attention task in which they were shown pairs of faces (one emotional and one neutral), while the direction of their gazes was recorded using electrooculography, and iii) a picture-viewing task, in which they rated standardized images with and without social content. During the ball-toss game, buprenorphine decreased perceived social rejection. During the attention task, the drug reduced initial attention to fearful facial expressions, without influencing attention to angry, happy, and sad faces. Finally, during the picture-viewing task, buprenorphine increased ratings of positivity of images with social content, without affecting ratings of nonsocial images. These results suggest that even at low doses, opioid analgesic drugs reduce responses to some types of negative social stimuli, while enhancing positive responses to social stimuli. This provides further support for the role of the opioid system in mediating responses to social rejection and social reward.

Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”), appears to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of two other “social” drugs on plasma oxytocin levels: methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin. In Study 1, 11 healthy adult volunteers attended three sessions during which they received methamphetamine (10mg or 20mg) or placebo under double blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin were measured at regular intervals throughout the sessions. In Study 2, 8 healthy adult volunteers attended a single session during which they received one beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither drug increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

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