Differential involvement of central cholinergic mechanisms in the aversive stimulus properties of morphine and amphetamine.

Abstract

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)