Discriminative stimulus effects of the nicotine antagonist mecamylamine in rats

The discriminative stimulus effects of the nicotine antagonist mecamylamine have been investigated to characterize further its behavioural effects and its interactions with (-)-nicotine. Rats were trained to discriminate the effects of mecamylamine from saline in a two-bar operant conditioning procedure with food reinforcers presented on a tandem schedule of reinforcement. Mecamylamine (3.5 mg/kg s.c.) acquired strong stimulus control over behaviour and there was only a small reduction in overall rates of responding. The mecamylamine stimulus generalized completely to some ganglion-blocking drugs (order of relative potency: pentolinium > mecamylamine > pempidine) but it did not generalize to other ganglion-blockers (hexamethonium, trimetaphan and chlorisondamine). The mecamylamine stimulus also failed to generalize to (-)-nicotine, to muscarinic antagonists (atropine and scopolamine) or to excitatory amino acid antagonists (dizocilpine, phencyclidine and D-CPPene). Mecamylamine, pempidine, hexamethonium, trimetaphan, (-)-nicotine, scopolamine, phencyclidine, dizocilpine and D-CPPene were tested up to doses that reduced overall rates of responding. Tests also showed that (-)-nicotine did not antagonize the response to mecamylamine. The discriminative stimulus produced by mecamylamine may originate at nicotinic receptors but whether these are located centrally or peripherally is unclear. There was no evidence that either muscarinic or excitatory amino acid receptors were involved in mediating the effect.