Role of medial prefrontal cortex in drug-cue associative memory and its functional interactions with the striatum

Abstract

Addicts are hypersensitive to the motivational properties of stimuli associated previously with drug taking, such as persons, places, or paraphernalia. The learned preference towards these stimuli has been studied in animals using preference conditioning or self-administration paradigms. Drug-cue associative learning is commonly used to investigate the motivational effects of psychoactive drugs. Drug-cue memories depend on the so-called striatum-corticolimbic circuit. Two different loops have been described. Reinstatement of cue-induced cocaine seeking is driven by interactions between the prelimbic (PL), nucleus accumbens core (NacC), BLA, and tegmental ventral area VTA. However, consolidation and extinction of conditioned cocaine seeking response is under the control of the infralimbic (IL), nucleus accumbens shell (NacSh) and basolateral amygdala (BLA). In the present research, we tested the role that specific regions in the mPFC play on the acquisition of cocaine-induced preference conditioning. Moreover, we assessed the functional changes that its deactivation cause on the striatum activity. We found that an IL deactivation promotes acquisition of cocaine-induced odor preference conditioning while a PL impairment prevents it. Regarding the changes of the striatum activity, neither of the unilateral deactivations of the mPFC affect c-Fos expression in NacSh. The neural activity in this region was related with the acquisition/expression of preference towards cocaine-related cue. PL deactivation, however, increased selectively c-Fos in NacC core. Finally, we did not find significant effects in c-Fos expression in DMS, DLS, VLS.