CORTICOTROPIN-RELEASING FACTOR-RECEPTOR BLOCKADE ENHANCES CONDITIONEDAVERSIVE PROPERTIES OF COCAINE IN RATS

The behavioral profile of corticotropin-releasing factor (CRF) in medi ating anxiogenic-like and aversive responses to stressors may be parti cularly relevant for dependence and withdrawal in drug-experienced org anisms Moreover stressful aspects of drug exposure sure in the drug na ive organism may also induce CRF system activation. In the present stu dies, the dependence of aversive properties of cocaine on activation o f endogenous CRF systems has been evaluated in rats using taste condit ioning and runway self-administration paradigms. Systemic cocaine admi nistration (20 mg/kg IP) produced a conditioned saccharin aversion whi ch was dose-dependently potentiated by central administration of the C RF receptor antagonist, D-phe CRF (12-41). In addition, IV cocaine adm inistration (0.75 mg/kg per injection IV) produced runway goal-box avo idance and conditioned place avoidance responses which were significan tly accelerated by CRF antagonist treatment. In contrast, CRF receptor stimulation using CRF itself abolished cocaine-induced increases in g oal latency in the runway paradigm. This generalized involvement of CR F systems in cocaine-related motivational/associative states is consis tent with the comprehensive role of CRF in mediating emotional respons es to non-drug stressors.