EFFECT OF ADRENALECTOMY ON COCAINE FACILITATION OF MEDIAL PREFRONTAL CORTEX SELF-STIMULATION

Adrenalectomy (ADX) is known to block the acquisition of intravenous c ocaine self-administration. A previous study therefore examined whethe r ADX decreases sensitivity of the 'brain reward system' in general, o r its response to cocaine in particular, by measuring thresholds for i ntracranial self-stimulation with and without concurrent cocaine admin istration. ADX had no effect on thresholds for lateral hypothalamic se lf-stimulation (LHSS) and did not alter the cocaine dose-response curv e for lowering the LHSS threshold. This result suggested that ADX does not affect sensitivity of the brain reward system. However, medial pr efrontal cortex (MPFC) appears to be an important site in the mediatio n of cocaine reinforcing effects, and MPFC self-stimulation (MPFCSS) i s mediated by a neural substrate that is largely independent of that w hich mediates LHSS. The present study therefore assessed whether ADX d iminishes cocaine facilitation of MPFCSS. It was found that the thresh old-lowering effect of cocaine (5.0, 10.0 and 20.0 mg/kg, i.p.) did no t differ between ADX rats maintained on 0.7% saline, ADX rats maintain ed on corticosterone (50 mu g/ml) in 0.7% saline, and sham-operated co ntrols. However, there was a trend toward desensitization of MPFCSS, i tself, following ADX in the group that did not receive corticosterone supplementation. Based on this observation, and the similar responses of MPFCSS and cocaine self-administration to noncontingent priming sti mulation, stress, and NMDA receptor antagonism, it is speculated that acquisition of MPFCSS and cocaine self-administration may be dependent upon a common sensitization process that is regulated by corticostero ne. (C) 1998 Elsevier Science B.V.