Abstract
Social defeat is considered the most representative animal model for studying the consequences of social stress. Intermittent social defeat (ISD) has proved to enhance the response to cocaine hedonic properties. In the present research, we evaluated if different social housing conditions, as housing with a familiar conspecific or with a female, exert a protective effect modulating the negative consequences of ISD as the increased sensitivity to cocaine and the induction of anxiety-like behavior. To achieve this objective, non-stressed or ISD OF1 male mice were divided into five different experimental groups according to their social environment: standard housing (four adult males per cage); male adolescent or adult in pairs (two males per cage); and adult males housed with a female for a short or long period (3 days vs. the whole duration of the study). Anxiety-like behavior was evaluated 19 days after the last episode of ISD using an elevated plus maze (EPM), and 24 h later the animals underwent a conditioned place preference paradigm (CPP) induced by a sub-threshold dose of cocaine (1 mg/kg). Following CPP, biological samples were taken to measure striatal levels of interleukin 6 (IL-6) and plasmatic levels of oxytocin (OT). Our results confirmed that ISD animals housed in standard condition displayed an anxious phenotype, developed CPP and had increased levels of IL-6 in the striatum. However, animals housed with a female or with a familiar male since adolescence did not develop CPP and were protected against the anxiogenic and neuroinflammatory potential of ISD stress. In the group of animals paired with a female throughout the experimental procedure, an increase in OT levels may have underlain this buffering effect, while the protective effect of being housed with a familiar male mouse seems to be related with a better resolution of the stress response. The present results expand our knowledge of the neurobiology of vulnerability to drug addiction and highlight the benefit of social support for recovery from the adverse effects of social stress.
Highlights
Drug addiction is a chronic disorder characterized by loss of control over the use of a substance and relapse during cessation attempts (Koob and Volkow, 2010; Volkow and Morales, 2015)
Intermittent social defeat (ISD) mice housed under the standard condition spent less time and less percentage of time in the open arms than their corresponding non-stress controls and compared to animals housed with a female for long and short terms (PF; p < 0.001)
Socially stressed mice under standard condition housing (STD-ISD) had higher conditioning score (CS) when compared to non-stressed animals in the same housing conditions (STD-nonISD, p < 0.05) and when compared to stressed animals housed with a female for long and short terms (PF, p < 0.01)
Summary
Drug addiction is a chronic disorder characterized by loss of control over the use of a substance and relapse during cessation attempts (Koob and Volkow, 2010; Volkow and Morales, 2015). The development of substance use disorder (SUD) is multifactorial, and the vulnerability to develop an addiction depends on a complex interplay between biological and environmental factors (Strickland and Smith, 2014). Social factors are powerful determinants of behavior and health status (Kessler et al, 2010; Ajonijebu et al, 2017). In this regard, there is a growing interest among researchers in studying the influence of social factors in addictive disorders (Neisewander et al, 2012). Positive social environments, such as strong family ties, involvement and attachment, are associated with lower rates of drug use and better prognosis during treatment (Stout et al, 2012; Litt et al, 2016)
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