beta-adrenergic antagonism alters the behavioral and neurochemical responses to cocaine.
The effects of the beta-adrenergic antagonist propranolol on the locomotor stimulating, neurochemical, and reinforcing effects of cocaine were examined in rats. In Experiment 1, propranolol (1, 3 and 10 mg/kg, IP) produced a dose-dependent increase in the motor stimulant effects of cocaine without affecting basal motor activity. Atenolol, a peripherally restricted beta 1 antagonist, and (+) propranolol, the inactive isomer of propranolol, did not alter cocaine-induced locomotion. In Experiment 2, propranolol was shown to augment significantly the increase in extracellular dopamine content in the nucleus accumbens that accompanies a cocaine challenge. Experiment 3 demonstrated that propranolol produced a dose-dependent decrease in cocaine self-administration. Atenolol (10 mg/kg, IP) reduced cocaine self-administration but to a much lesser extent than propranolol. Experiment 4 demonstrated that coadministration of propranolol and cocaine did not alter the levels of cocaine in the brain and plasma achieved by cocaine administration alone. These data suggest that the blockade of beta-adrenergic receptors potentiates cocaine-induced elevation of dopamine transmission in the nucleus accumbens, which is associated with an increase in cocaine-induced motor activity and a decrease in cocaine self-administration.
Harris
G C
GC
Alcohol and Drug Abuse Program, Washington State University, Pullman, WA 99164-6520, USA.
Hedaya
M A
MA
Pan
W J
WJ
Kalivas
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol; D003042:Cocaine; D004298:Dopamine