Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas.

Rana El Rawas,Sabine Klement,Georg Dechant,Ahmad Salti,Michael Fritz,Gerald Zernig,Alois Saria

doi:10.3389/fnbeh.2012.00008

Rana El Rawas, Sabine Klement + Show 5 more

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https://doi.org/10.3389/fnbeh.2012.00008

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Abstract

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction.

Highlights

Drug dependence is a multifactorial disorder resulting from an interaction between genetic, social, and environmental factors (Kreek et al, 2005; Enoch, 2006)
In the present study we investigated the expression of FosB/ FosB and pCREB proteins using immunohistochemistry in mesocorticolimbic areas in brains of (1) naïve rats, (2) rats that underwent cocaine conditioned place preference (CPP) followed by saline extinction, and (3) rats that underwent cocaine CPP followed by social interaction during saline extinction
REINSTATEMENT OF COCAINE CPP: EFFECT OF SOCIAL INTERACTION ON THE EXPRESSION OF pCREB TRANSCRIPTION FACTOR Given that CREB and FosB usually produce opposite effects on either the expression of numerous genes or a number of behavioral phenotypes, we investigated pCREB expression in brain areas involved in drug rewarding effects of rats that did not undergo the reinstatement test using immunohistochemistry. pCREB expression was significantly different between treatments in the following brain areas (Figure 4): Cg1 [OneWay analyses of variance (ANOVA), treatment effect: P < 0.05] and accumbens shell (AcbSh) [One-Way ANOVA, treatment effect: P < 0.05]

Summary

Introduction

Drug dependence is a multifactorial disorder resulting from an interaction between genetic, social, and environmental factors (Kreek et al, 2005; Enoch, 2006). There is little research on how social interaction, if offered as an alternative to drug consumption, affects neural circuits involved in drug reinforcement and substance dependence. We have recently shown that only four social interaction episodes (15 min each) with a male early-adult conspecific as an alternative (i.e., non-drug-associated) stimulus completely reversed conditioned place preference (CPP) for cocaine (15mg/kg i.p.) and were even able to inhibit cocaine-induced reinstatement of cocaine CPP (Fritz et al, 2011a). Social interaction during extinction of cocaine CPP reversed cocaine CPP-reinstatement-associated Zif268 expression in the nucleus accumbens shell, the central and basolateral amygdala, and the ventral tegmental area (Fritz et al, 2011a). We have shown that the sigma receptor antagonist BD1047 enhances reversal of conditioned place preference from cocaine to social

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