Cocaine effects on brain noradrenergic neurons of anesthetized and unanesthetized rats

The present study characterized and quantified the effects of systemically administered cocaine on spontaneous, sensory-evoked and stress-elicited activity of noradrenergic locus coeruleus (LC) neurons of anesthetized and unanesthetized rats. Cocaine (0.1-3.0 mg/kg, i.v.) decreased LC spontaneous discharge rate and discharge evoked by repeated sciatic nerve stimulation in halothane-anesthetized rats. In unanesthetized rats cocaine (0.3-10.0 mg/kg, i.v.) also decreased LC spontaneous discharge rate and LC discharge evoked by repeated auditory stimulation. However, analysis of variance revealed a statistically significant shift to the right in the cocaine dose-response curves for effects on tonic 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-releasing factor (3.0 micrograms in 3.0 microliters) or by hemodynamic stress elicited by i.v. nitroprusside infusion. The present findings demonstrate that cocaine has similar effects on LC neurons of anesthetized and unanesthetized rats but that it is less potent in unanesthetized rats. These effects of cocaine at noradrenergic cell bodies acting in concert with its effects at noradrenergic terminals in LC target regions may be important in the overall action of cocaine on arousal and cortical information processing.