Reinstatement of cocaine seeking in rats by the pharmacological stressors, corticotropin-releasing factor and yohimbine: role for D1/5 dopamine receptors

Two pharmacological stressors commonly used in the study of stress-induced reinstatement of drug seeking are central injections of the stress peptide, corticotropin-releasing factor (CRF), and systemic administration of the alpha(2)-adrenoceptor antagonist, yohimbine. Despite the widespread use of these stressors, the neurochemical systems mediating their ability to reinstate cocaine-seeking behaviour have not been fully characterized. The present study was designed to characterize the role, specifically, of dopamine transmission in the reinstating effects of CRF and yohimbine on cocaine seeking. Male Long-Evans rats were trained to self-administer cocaine (0.23 mg/kg/infusion) for 8-10 days. Subsequently, responding for drug was extinguished, and tests for CRF- (0.5 mu g; i.c.v.) and yohimbine-induced (1.25 mg/kg; i.p.) reinstatement were conducted following pretreatment with the dopamine D1/5 receptor antagonists, SCH23390 (0.05, 0.1 mg/kg; i.p.) and/or SCH31966 (0.2 mg/kg; i.p.), and the D2/3 receptor antagonist, raclopride (0.25, 0.5 mg/kg; i.p.). Pretreatment with SCH23390, but not raclopride, blocked CRF-induced reinstatement of cocaine seeking. Pretreatment with SCH23390 and SCH31966, but not raclopride, blocked yohimbine-induced reinstatement of cocaine seeking. These findings demonstrate that transmission at D1/5, but not D2/3, receptors mediates the reinstatement of cocaine seeking induced by CRF and yohimbine.