Abstract

Cocaine-seeking behavior can be investigated in rodents using the conditioned place preference (CPP) paradigm. CPP can be extinguished and then reactivated using cocaine priming. To study the role of dopaminergic receptors in CPP reinstatement, CPP was induced in Swiss mice using cocaine (30 mg/kg ip) and extinguished with saline. CPP reactivation was examined by treatment with the D1 receptor antagonist SCH23,390 (0.03-1 mg/kg), the D2 antagonist raclopride (0.1-3 mg/kg) or the D3 antagonist U-99,194A (20-40 mg/kg), alone or before cocaine (15 mg/kg). Cocaine priming reactivated CPP up to 220% of the post-conditioning response. SCH23,390 and raclopride induced, alone at 0.3 mg/kg, reactivation of cocaine-induced CPP, but only SCH23,390 blocked the cocaine-induced reactivation. U99,194A failed to promote CPP reactivation alone or to affect the cocaine response. CPP reactivation involving contextual learning could be induced using a single-reconditioning session after extinction. Treatment with cocaine or raclopride, but not SCH23,390, induced CPP reactivation. Finally, the emotional state of mice was tested during reactivation under drug treatments in the elevated maze procedure and an anxiety state was measured after 0.3 mg/kg SCH23,390. These observations showed that in cocaine-conditioned animals and then extinguished, blockade of D1 receptors induces an anxiogeniclike state, able to promote a cocaine-sensitive CPP reactivation. Blockade of D2 receptor promoted a cocaine-mimetic CPP reactivation. Therefore, two different psychological states underlie CPP reactivation by drug priming: a 'drug craving CPP' induced by dopamine systems-mediated anxiety and a 'drug retrieval CPP' promoted by incentive learning processes.