Nonhuman primate models of social behavior and cocaine abuse

Abstract

Rationale Although cocaine is often abused in social situations, very few animal studies examine the effects of cocaine in the context of social behavior. Objectives This review highlights studies investigating the behavioral effects of cocaine in the context of social housing conditions using nonhuman primates. In addition, this review presents recent findings examining the effects of self-administering cocaine on social behavior and the effects of manipulations hypothesized to be stressful or enriching on the interactions between cocaine reinforcement and social rank. The following dependent variables are examined: 1) cocaine-induced changes in social behavior and 2) cocaine self-administration in cynomolgus monkeys of varying social ranks. The independent variables examined include several environmental and pharmacological manipulations. Conclusions The studies reviewed here indicate that several variables can differentially affect cocaine self-administration when studied in a social context, rather than in individually housed animals. These variables include the social rank and sex of the individual, drug history, the nature of the “fear”-inducing manipulation, and the reliability of cortisol as an appropriate measure of “stress.” While the inclusion of socially housed animals necessitates larger sample sizes, animal models incorporating social behavior are more homologous to the human condition and should be implemented when possible.

Animal models of social contact and drug self-administration

“…Studies conducted in rodents (Blanchard et al, 1987; Pohorecky, 2006, 2008) and non-human primates (McKenzie-Quirk and Miczek, 2008) indicate that home-cage ethanol consumption is linked to dominance rank, with the highest rates of consumption in subordinate subjects. Such findings are consistent with the notion that home-cage, free-consumption models may capture the effects of stress induced by social isolation and social hierarchies (for more on the role of social dominance in drug abuse, see review by Nader et al, 2012). …”

“…Preclinical animal studies have successfully modeled many of these factors and have consistently revealed their role in drug self-administration. For example, studies using rodents and nonhuman primates have revealed that social stress and social isolation increase, whereas social enrichment and social dominance decrease, drug self-administration across a wide variety of drug classes and schedules of reinforcement (see reviews by Burke and Miczek, 2014; Nader et al, 2012; Stairs and Bardo, 2009). That drug use in humans is similarly affected by distal social factors (e.g., Gordon, 2002) supports the validity of these models for predicting human drug use and for evaluating putative interventions for drug use disorders.…”

Effects of Oral and Intravenous Administration of Buspirone on Food–Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

“…buspirone also reported no decreases in cocaine choice. The major finding from this study was that monkeys living in what has been hypothesized to be an enriched environment (Nader et al, 2012a) showed decreases in cocaine choice following acute buspirone administration. As in previous studies Mello et al, 2013), buspirone exhibited behavioral effects that interfered with responding early in the experimental session.…”

“…Little is known about the effects of environmental variables on specific D2-like receptor subtypes; it may be that the environmental variables associates with the social hierarchy differentially affect D 2 , D 3 , and D 4 receptors. Considering the well-documented ability of environmentally derived stress and enrichment to modulate cocaine self-administration (see, eg, Nader et al, 2012a;Bardo et al, 2013) the effects of environmental variables on D 3 and D 4 receptors warrant further study.…”

Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers

“…Since monkey studies have shown that striatal D2/D3 receptor binding can be changed by environmental factors in social hierarchy [16] (though see [17] suggesting that after differences in D2/D3R binding due to social status have been established, this cannot be changed anymore), future studies in humans investigating whether changes in SES covary with changes in striatal D2/D3R availability are relevant for prevention interventions towards improving health outcomes in individuals who are socially deprived.…”