BETA-ADRENERGIC ANTAGONISM ALTERS THE BEHAVIORAL AND NEUROCHEMICAL RESPONSES TO COCAINE

The effects of the beta-adrenergic antagonist propranolol on the locom otor stimulating, neurochemical, and reinforcing effects of cocaine we re examined in rats. In Experiment 1, propranolol (1, 3 and 10 mg/kg, IF) produced a dose-dependent increase in the motor stimulant effects of cocaine without affecting basal motor activity. Atenolol, a periphe rally restricted beta(1) antagonist, and (+) propranolol, the inactive isomer of propranolol, did not alter cocaine-induced locomotion. In E xperiment 2, propranolol was shown to augment significantly the increa se in extracellular dopamine content in the nucleus accumbens that acc ompanies a cocaine challenge. Experiment 3 demonstrated that propranol ol produced a dose-dependent decrease in cocaine self-administration. Atenolol (10 mg/kg, IF) reduced cocaine self-administration but to a m uch lesser extent than propranolol. Experiment 4 demonstrated that coa dministration of propranolol and cocaine did Mot alter the levels of c ocaine in the brain and plasma achieved by cocaine administration alon e. These data suggest that the blockade of beta-adrenergic receptors p otentiates cocaine-induced elevation of dopamine transmission in the n ucleus accumbens, which is associated with an increase in cocaine-indu ced motor activity and a decrease in cocaine self-administration.