Nicotine and arecoline as discriminative stimuli: Involvement of a non-cholinergic mechanism for nicotine

The cholinergic innervation of central muscarinic (MCh) and nicotinic (NCh) receptors was evaluated by studying the interaction of physostigmine with the discriminative stimulus (DS) effects of arecoline and nicotine. Rats were trained to discriminate either arecoline (1.74 mg/kg) or nicotine (1.14 mg/kg) from saline using a two-lever, milk reinforced, operant task. Physostigmine (0.125 mg/kg) pretreatment potentiated, and when administered alone (0.25 mg/kg), generalized with the DS induced by arecoline. In contrast, physostigmine, at the same dose, neither potentiated nor generalized with the DS effects of nicotine. These findings provide evidence that central muscarinic receptors are cholinergically innervated (physiologic) while central nicotinic receptors are not cholinergically innervated but are cholinoceptive (pharmacological).