RESUMEN
RATIONALE: The neural circuitry subserving cocaine-seeking after extinction vs abstinence alone requires different constituent brain structures. Spontaneous recovery of cocaine-seeking, a model, which incorporates both extinction and abstinence, depends on an unknown neural circuit. OBJECTIVES: The present study examined the hypothesis that the spontaneous recovery of cocaine-seeking would require overlapping but distinct neural circuits compared to models that incorporate either extinction or abstinence alone. MATERIAL AND METHODS: Rats were trained to self-administer cocaine (0.2 mg/inf), then responding on the cocaine-paired lever was extinguished, followed by an additional period of abstinence in the home cage. Finally, rats were returned to the self-administration context for a test of spontaneous recovery (SR TEST). Just before the SR TEST, discrete brain regions were inactivated with a GABA agonist cocktail (1 mM baclofen + 0.1mM muscimol) to determine the relative importance of these brain regions in the spontaneous recovery of cocaine-seeking. RESULTS: The inactivation of the ventromedial prefrontal cortex (vPFC) enhanced cocaine-seeking, whereas the inactivation of the basolateral amygdala (BLA) attenuated spontaneous recovery. Inactivation of the nucleus accumbens core (Core) resembled the effects of BLA inactivation, but these results were confounded by an inhibitory effect of the vehicle treatment. Finally, the spontaneous recovery of cocaine-seeking was unaltered by manipulations of the dorsomedial prefrontal cortex (dPFC) and the nucleus accumbens shell (Shell). CONCLUSIONS: The neural circuitry subserving cocaine-seeking behavior in a spontaneous recovery model requires the BLA and possibly the Core, like extinction models. In addition, this behavior is subject to regulation by vPFC, in a manner functionally opposite to that of the BLA.