COCAINE EFFECTS ON BRAIN NORADRENERGIC NEURONS OF ANESTHETIZED AND UNANESTHETIZED RATS

The present study characterized and quantified the effects of systemic ally administered cocaine on spontaneous, sensory-evoked and stress-el icited activity of noradrenergic locus coeruleus (LC) neurons of anest hetized and unanesthetized rats. Cocaine (0.1-3.0 mg/kg, i.v.) decreas ed LC spontaneous discharge rate and discharge evoked by repeated scia tic nerve stimulation in halothane-anesthetized rats. In unanesthetize d rats cocaine (0.3-10.0 mg/kg, i.v.) also decreased LC spontaneous di scharge rate and LC discharge evoked by repeated auditory stimulation. However, analysis of variance revealed a statistically significant sh ift to the right in the cocaine dose-response curves for effects on to nic and evoked LC discharge in unanesthetized compared to anesthetized rats. Thus, cocaine was somewhat less potent in inhibiting tonic and evoked discharge of unanesthetized rats compared to anesthetized rats. In anesthetized rats cocaine (1.0 mg/kg) did not affect LC activation by intracerebroventricularly (i.c.v.) administered corticotropin-rele asing factor (3.0 mug in 3.0 mul) or by hemodynamic stress elicited by i.v. nitroprusside infusion. The present findings demonstrate that co caine has similar effects on LC neurons of anesthetized and unanesthet ized rats but that it is less potent in unanesthetized rats. These eff ects of cocaine at noradrenergic cell bodies acting in concert with it s effects at noradrenergic terminals in LC target regions may be impor tant in the overall action of cocaine on arousal and cortical informat ion processing.