Central sites and mechanisms of action of nicotine.

Research conducted in this laboratory over the last ten years has been directed towards determining possible CNS sites and mechanisms by which nicotine is producing its psychopharmacological effects. To accomplish these goals, a drug discrimination paradigm was utilized in which rats were trained to detect nicotine using a two-lever operant procedure. In this situation nicotine acted as a discriminative stimulus (DS) to correct lever responding. In other words rats had to be able to differentiate nicotine's effects from saline in order to obtain a food reinforcement. The ability of nicotine to exert its DS effects appear to be dependent upon a stimulation of central nicotinic-cholinergic receptors which are stereospecific to (-)-nicotine. Interestingly, the nicotine DS could not be mimicked or potentiated by elevating brain acetylcholine levels centrally suggesting that the receptor action was non-cholinergic. Additional studies indicated that nicotine is acting at both reticular formation and hippocampus sites. The hippocampal site of nicotine action also appears to be dependent on a dopamine neuron connection as well.