A comparison of nicotine and structurally related compounds as discriminative stimuli

1 Of seven nicotine-like compounds tested as discriminative stimuli in the rat, only 3-pyridyl-methylpyrollidine (3-PMP) generalized to the stimulus effects of nicotine. 2 3-PMP caused equivalent nicotine-like responding at a dose (800 microgram/kg) approximately 4 times that used for the original nicotine discrimination (200 microgram/kg). The ED50 for 3-PMP was about 5 times that for nicotine. 3 Testing of the compounds as possible antagonists of the nicotine-elicited cue were negative. 4 The nicotine-like cue produced by an 800 microgram/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. 5 Mecamylamine blocked the stimulus-effects of 3-PMP (800 microgram/kg) and of nicotine (200 microgram/kg) with an ED50 of 0.32 and 0.20 microgram/kg respectively.