SYMPATHETIC-NERVE RESPONSES ELICITED BY COCAINE IN ANESTHETIZED AND CONSCIOUS RATS

Recent evidence suggests that cocaine decreases rather than increases sympathetic nerve discharge (SND). The purpose of the present study wa s to provide the first complete characterization of the dose-response relationships of cocaine (0.005-3 mg/kg, IV) for arterial pressure, he art rate, and lumbar, splanchnic, or renal SND in pentobarbital-anesth etized rats. Cocaine was also tested in conscious rats. In pentobarbit al-anesthetized rats cocaine elicited prolonged (lasting up to 56 min) , dose-dependent decreases in SND on all three nerves. The splanchnic nerve was significantly more sensitive to the inhibitory actions of co caine than was the lumbar nerve. Cocaine increased arterial pressure a nd elicited bradycardia at doses above 0.5 mg/kg. Comparison of the do se-response curves of cocaine for splanchnic SND in sham-operated and sinoaortically deafferentated (SAD) rats showed that the baroreceptor reflex made only a minor contribution to the magnitude of sympathoinhi bitory response. However, the duration of the sympathoinhibitory respo nse was significantly shorter in SAD than in sham animals. In consciou s rats, cocaine (0.1 and 1.0 mg/kg) elicited a pattern of neural and c ardiovascular responses similar to that seen in anesthetized rats, exc ept that the prolonged sympathoinhibitory responses were preceded by a brief (lasting < 10 s) increase in SND. From these data we conclude t hat cocaine produces prolonged decreases in SND in conscious and anest hetized rats. These sympathoinhibitory responses do not appear to resu lt from baroreceptor reflex activation and may involve a central mecha nism of action.