A COMPARISON OF NICOTINE AND STRUCTURALLY RELATED COMPOUNDS AS DISCRIMINATIVE STIMULI

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Abstract
Of seven nicotine‐like compounds tested as discriminative stimuli in the rat, only 3‐pyridyl‐meth‐ylpyrollidine (3‐PMP) generalized to the stimulus effects of nicotine. 3‐PMP caused equivalent nicotine‐like responding at a dose (800 μg/kg) approximately 4 times that used for the original nicotine discrimination (200 μg/kg). The ED50 for 3‐PMP was about 5 times that for nicotine. Testing of the compounds as possible antagonists of the nicotine‐elicited cue were negative. The nicotine‐like cue produced by an 800 μg/kg injection of 3‐PMP was effectively blocked by mecamylamine but not by hexamethonium or atropine. Thus, 3‐PMP appears to produce generalization to the nicotine cue via action on central nicotinic‐cholinoceptors as has been previously reported for the nicotine discriminative stimulus. Mecamylamine blocked the stimulus‐effects of 3‐PMP (800 μg/kg) and of nicotine (200 μg/kg) with an ED50 of 0.32 and 0.20 mg/kg respectively.