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Neuropsychopharmacology (1996) 14 195-204.
 -Adrenergic Antagonism Alters the Behavioral and Neurochemical Responses to Cocaine
Glenda C Harris1, Mohsen A Hedaya2, Wei-Jian Pan and Peter Kalivas Ph.D1 |
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1From the Alcohol and Drug Abuse Program, Washington State University, Pullman, WA
2The Department of Pharmaceutical Sciences, Washington State University, Pullman, WA
Correspondence: Peter Kalivas, Ph.D, Alcohol and Drug Abuse Program, Department VCAPP, Washington State University, Pullman, WA 99164-6520
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ABSTRACT
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The effects of the -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 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 -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.
Keywords: Cocaine; Propranolol; Dopamine; Locomotion; Self-administration; Dopamine |
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