Differential involvement of central cholinergic mechanisms in the aversive stimulus properties of morphine and amphetamine.
Previously, it was reported that pretreatment with the centrally-acting cholinergic antagonist atropine, but not the peripherally-acting antagonist, methyl-atropine, may serve to attenuate the positive reinforcing properties of morphine and conversely, to enhance those of amphetamine as evidenced within a drug self-administration paradigm in rats. In parallel, evidence from several sources would suggest that there may be a functional relationship between the neurochemical mechanisms mediating these drugs' positive reinforcing properties and their seemingly paradoxical capacity to act as aversive stimuli, as evidenced within a conditioned taste aversion (CTA) paradigm. Accordingly, the present study undertook to examine whether a similar differential involvement of central cholinergic mechanisms established for these drugs' positive reinforcing effects may be obtained for morphine and amphetamine-induced CTA. Using a conventional CTA paradigm, animals were pretreated with either intraperitoneal (IP) atropine or methyl-atropine (0.6 mg/kg) 40 minutes prior to consuming a novel 0.1% saccharin solution. This taste stimulus was paired with IP injection of 15 mg/kg morphine or vehicle. Results showed that atropine (but not methyl-atropine) pretreatment served to attenuate the morphine CTA. In a second experiment, atropine-pretreatment failed to attenuate, and may have slightly potentiated, a CTA induced by 1 mg/kg amphetamine. Atropine pretreatment did not affect a CTA induced by the emetic agent, lithium chloride. Pretreatment with the peripherally-acting methyl-atropine had no effect on the amphetamine CTA and served, if anything, to slightly attenuate the lithium chloride CTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Centre for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
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D000109:Acetylcholine / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D013649:Taste / Q000187:drug effects / Q000502:physiology
D001286:Atropine Derivatives; D009020:Morphine; D001285:Atropine; C006649:methylatropine; D000661:Amphetamine; D000109:Acetylcholine