THE EFFECTS OF IN-VIVO COCAINE ON NOREPINEPHRINE-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN RAT-BRAIN

We examined the effects of a cocaine challenge on behavioral stimulati on and NE-stimulated [H-3]inositol-l-phosphate (IP1) formation in rat cerebral cortex after single (high dose) or repeated (low dose) cocain e administration. As previously reported, single high dose (40 mg/kg, IP) and repeated low dose (10 mg/kg, 8 IP injections) administrations of cocaine resulted in behavioral sensitization to a challenge injecti on of cocaine (10 mg/kg). In saline-pretreated animals, the acute coca ine challenge significantly potentiated the NE-stimulated [H-3]IP1 for mation as compared with the saline challenge, while in cocaine-pretrea ted animals, NE-stimulated phosphoinositide (PI) turnover was not sign ificantly altered. These results suggest that although some of the acu te effects of cocaine may be mediated by enhanced alpha(1)-adrenergic receptor-linked PI hydrolysis, behavioral sensitization does not invol ve the alpha(1)-adrenergic receptor-linked PI signal transduction syst em.