The kappa-opioid receptor agonist U-69593 attenuates cocaine-induced behavioral sensitization in the rat.
The effects of treatment with the selective kappa-opioid receptor agonist U-69593 upon cocaine-induced changes in locomotor activity and stereotypy were examined in rats. U-69593 (0.16 mg/kg s.c.) administered either acutely or chronically attenuated both the motor stimulant effect and stereotypy produced by an acute injection of cocaine (20 mg/kg i.p.). Daily cocaine treatment resulted in sensitization to both effects of cocaine. In contrast, no such sensitized responses were seen in animals which had received U-69593 either prior to or in conjunction with daily cocaine treatment. These data demonstrate that activation of kappa-opioid receptors attenuates the acute and chronic effects of cocaine on locomotor activity and stereotypy. Given the inhibitory effects ascribed to both exogenous and endogenous kappa-opioid agonists upon dopamine release in the mesolimbic dopaminergic system, it is suggested that this action may underlie the observed effects of U-69593 on cocaine-induced changes in locomotor activity and stereotypy.
Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse, Baltimore, MD 21224.
C A
CA
Heidbreder
S R
SR
Goldberg
T S
TS
Shippenberg
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D000700:Analgesics; D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D003042:Cocaine; C045444:U 69593