The effects of in vivo cocaine on norepinephrine-stimulated phosphoinositide hydrolysis in rat brain.

We examined the effects of a cocaine challenge on behavioral stimulation and NE-stimulated [3H]inositol-1-phosphate (IP1) formation in rat cerebral cortex after single (high dose) or repeated (low dose) cocaine 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 injection of cocaine (10 mg/kg). In saline-pretreated animals, the acute cocaine challenge significantly potentiated the NE-stimulated [3H]IP1 formation as compared with the saline challenge, while in cocaine-pretreated animals, NE-stimulated phosphoinositide (PI) turnover was not significantly altered. These results suggest that although some of the acute effects of cocaine may be mediated by enhanced alpha 1-adrenergic receptor-linked PI hydrolysis, behavioral sensitization does not involve the alpha 1-adrenergic receptor-linked PI signal transduction system.