Differential effects of baclofen and oxytocin on the increased ethanol consumption following chronic psychosocial stress in mice

Abstract

Chronic stress is known to enhance the susceptibility for addiction disorders including alcoholism. While these findings have been recapitulated in animal models, the majority of these studies have utilized non-social rather than social stress paradigms; the latter of which are believed to be more relevant to the human situation. Therefore, the major aim of this study was to investigate, if 14 days of chronic subordinate colony housing (CSC), a pre-clinically validated psychosocial stress paradigm relevant for human psychiatric and somatic disorders, enhances ethanol (EtOH) consumption in male mice. To assess this, we employed the well-established two-bottle free-choice paradigm where mice were given access to water and 2, 4, 6 and 8% EtOH solutions (with the concentrations increasing each fourth day) following termination of the stress procedure. After 14 days of CSC, stressed mice consumed significantly more EtOH at all concentrations tested and displayed increased EtOH preference at concentrations of 6 and 8%. This effect was not due to an altered taste preference in CSC mice as assessed by saccharine- and quinine-preference tests, but was accompanied by increased anxiety-related behavior. Systemic administration of baclofen (2.5 mg/kg) or oxytocin (OXT; 10 mg/kg) reduced the EtOH intake in single housed control (baclofen, OXT) and CSC (baclofen) mice, whereas intracerebroventricular OXT (0.5 μg/2 μl) was ineffective in both groups. Taken together, these results suggest that (i) chronic psychosocial stress enhances EtOH consumption, and (ii) baclofen and OXT differentially affect EtOH intake in mice.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

“…Along the same line, Peters and colleagues were able to show that shorter stress periods produced the same effect. In fact, following 14 days of chronic subordinate colony housing, the CSC mice consumed significantly more ethanol than SHC controls (Peters et al 2013). However, to our knowledge, this is the first study to report that CSC housing-induced chronic psychosocial stress produces reinstatement of ethanol-induced CPP behavior.…”

“…This has been recapitulated in animal models, but most studies have utilized non-social rather than social stress paradigms, of which the latter are believed to be more relevant to the human situation, mainly for a lack of appropriate animal models. Nevertheless, recent studies have found that chronic psychosocial stress in mice induces an anxiogenic-like phenotype and enhances alcohol consumption and preference (Bahi 2013a;Peters et al 2013) as well as ethanol-induced conditioned place preference (EtOH-CPP) (Bahi 2013a). Animal studies reporting a positive correlation between stress and alcohol consumption suggest that drinking may take place in response to chronic stress if it is perceived as unavoidable (Nash and Maickel 1988;Volpicelli 1987), when alternative resources are lacking, when alcohol is accessible, and when the individual believes that alcohol will help to reduce the stress (Jennison 1992).…”

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…Es wird spekuliert, dass sich die Wirkung von Baclofen durch die Aktivierung von Oxytocinneuronen im PVN entfaltet [49,50].…”

Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice

“…Importantly, McGregor and Bowen reported lasting reduction (at least 6 weeks) in "Vodka Cruiser" preference (relative to 3% sucrose) in male and female alcohol preferring rats following a single administration of oxytocin (1 mg/kg) [4]. Recently, Peters and colleagues reported that, following 2 weeks of a two-bottle free choice continuous access of increasing concentrations of ethanol, systemic oxytocin (10 mg/kg) administration reduced the alcohol intake in single housed mice but not in stressed counterparts [27]. In humans, and compared to placebo, intranasal oxytocin given twice daily for 3 days in alcohol-dependent subjects, during a double-blind clinical trial, reduced alcohol withdrawal symptoms and reduced the amount of lorazepam administered "as needed" during detoxification [6].…”