Abstract
The reorientation away from drugs of abuse and toward social interaction is a highly desirable but as yet elusive goal in the therapy of substance dependence. We could previously show that cocaine preferring Sprague-Dawley rats which engaged in only four 15 min episodes of dyadic social interaction (DSI) did not reacquire and reexpress cocaine conditioned place preference (CPP) after a single cocaine exposure. In the present study, we investigated how strong this preventive effect of DSI is. In corroboration of our previous findings in rats, four 15 min DSI episodes prevented the reacquisition/reexpression of cocaine CPP in mice. However, this effect was only observed if only one cocaine conditioning session (15 min) was used. If mice were counterconditioned with a total of four cocaine sessions, the cocaine CPP reemerged. Interestingly, the opposite also held true: in mice that had acquired/expressed cocaine CPP, one conditioning session with DSI did not prevent the persistence of cocaine CPP, whereas four DSI conditioning sessions reversed CPP for 15 mg/kg intraperitoneal cocaine. Of note, this cocaine dose was a strong reward in C57BL/6J mice, causing CPP in all tested animals. Our findings suggest that both the reversal (reconditioning) of CPP from cocaine to DSI as well as that from DSI to cocaine requires four conditioning sessions. As previously shown in C57BL/6 mice from the NIH substrain, mice from the Jackson substrain also showed a greater relative preference for 15 mg/kg intraperitoneal cocaine over DSI, whereas Sprague-Dawley rats were equally attracted to contextual stimuli associated with this cocaine dose and DSI. Also in corroboration of previous findings, both C57BL/6J mice and experimenters several generations removed from the original ones produced CPP for DSI to a lesser degree than Sprague-Dawley rats. Our findings demonstrate the robustness of our experimental model across several subject- and experimenter generations in two rodent genus (i.e., mouse and rat) and allow the quantification of the strength (i.e., persistence) of the preventive effect of DSI against the reacquisition/reexpression of cocaine CPP, arguably a model for cocaine relapse.
Highlights
The reorientation away from drugs of abuse and toward social interaction is a highly desirable but as yet mostly elusive goal in the therapy of substance dependence (Zernig et al, 2007, 2013; Zernig and Pinheiro, 2015), warranting its neurobiologic investigation
The present results demonstrate that even in dyadic social interaction (DSI) counterconditioned mice, a subsequent cocaine history that is long enough is sufficient to overcome the protective effect of DSI
If these mice were exposed to cocaine in its associated compartment for one time only, the reacquisition/reexpression of cocaine conditioned place preference (CPP) was prevented at the group mean level (Figure 2A, top row; p = 0.013 for coc CPP vs. coc RE-CPP), confirming our initial findings obtained in rats (Fritz et al, 2011b)
Summary
The reorientation away from drugs of abuse and toward social interaction is a highly desirable but as yet mostly elusive goal in the therapy of substance dependence (Zernig et al, 2007, 2013; Zernig and Pinheiro, 2015), warranting its neurobiologic investigation. Many would argue that such a remarkable preventive/protective effect of social interaction against cocaine relapse could hardly be found in human addicts who are often impaired in their social interaction and find interacting with others more aversive than non-drug-dependent individuals (see e.g., Zernig et al, 2000, 2003; Nutt et al, 2010). If one accepts that ‘‘much less social flexibility’’ in the mouse may model ‘‘impaired social interaction’’ in human addicts to some degree, the mouse genus would confer greater translational power to animal experimentals on DSI as a non-drug alternative to drugs of abuse
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