mu-, delta- and kappa-opioid receptor agonists do not alter the discriminative stimulus effects of cocaine or d-amphetamine in rats.
Opioid receptor agonists can modulate the activity of dopamine neurons and could therefore, modify the behavioral effects of drugs that act through the dopamine systems, such as d-amphetamine and cocaine. We tested the ability of agonists selective for the mu- (morphine, methadone, buprenorphine, nalbuphine and heroin), delta-(DPDPE and SCH32615), and kappa- (U69593 and bremazocine) opioid receptors to alter the discriminative stimulus effects of d-amphetamine and cocaine in rats. Separate groups of male Sprague-Dawley rats were trained to discriminate between 1.0 mg/kg d-amphetamine or 10 mg/kg cocaine from saline. Rats were pretreated with vehicle or an agonist, then dose-response curves for d-amphetamine or cocaine were generated. None of the opioid agonists changed significantly the ED50 values of cocaine and d-amphetamine. As a positive control, we tested for antagonism of these effects by the D1 and D2 dopamine receptor antagonists, SCH23390 and eticlopride, respectively. Both antagonists at least partially attenuated the stimulus effects of both training drugs. Our results suggest that any modulation of dopaminergic neurotransmission by the agonists tested in the present study is not sufficient to affect the stimulus effects of d-amphetamine and cocaine in rats.
Woolfolk
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Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. dwoolfo@emory.edu
Holtzman
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D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D016001:Confidence Intervals; D003463:Cues; D003913:Dextroamphetamine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007206:Individuality; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*
D018492:Dopamine Antagonists; D011957:Receptors, Opioid; D003042:Cocaine; D003913:Dextroamphetamine