Noradrenergic antagonism enhances the conditioned aversive effects of cocaine.
The propensity to self-administer cocaine may be a function of both its positively reinforcing and aversive effects, with the latter acting as a limiting factor on overall drug taking. However, relative to what is known about the physiological underpinnings of cocaine's positively reinforcing effects, little is known about its aversive effects. There is some evidence that cocaine's aversive effects, as indexed in the conditioned taste aversion (CTA) preparation, are catecholaminergically mediated, i.e., through cocaine's actions on the dopaminergic and noradrenergic neurotransmitter systems. Although limited evidence suggests a role for dopamine, there has yet to be a direct assessment of noradrenergic involvement. To better characterize a role for this system, cocaine-induced CTAs (10, 18 and 32 mg/kg) were conducted under conditions of antagonism at the norepinephrine alpha(1) and beta receptors using prazosin (0.3 mg/kg; Experiment 2) and propranolol (10 mg/kg; Experiment 3), respectively, at doses that were determined to be non-aversive (Experiment 1). In each case of noradrenergic antagonism, CTAs with cocaine were not attenuated, suggesting that this drug's conditioned aversive effects are mediated by non-noradrenergic NT activity. Furthermore, prazosin and propranolol administration appeared to facilitate the conditioned aversive effects of cocaine. The implications of these findings in regards to other neurochemical processes are discussed.
Freeman
Kevin B
KB
Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, United States. kfreeman@psychiatry.umsmed.edu
Verendeev
Andrey
A
Riley
Anthony L
AL
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013649:Taste / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D011433:Propranolol; D003042:Cocaine; D009638:Norepinephrine; D011224:Prazosin