Brain regions mediating the discriminative stimulus effects of nicotine in rats

The involvement of cerebral regions in the discriminative stimulus (DS) effects of nicotine was studied using rats. Substitution tests with nicotine administered into the medial prefrontal cortex, nucleus accumbens, and ventral tegmental area, all of which are located on the mesolimbocortical dopaminergic neurons, and into the dorsal hippocampus and medial habenular nucleus, which possess high densities of nicotinic cholinergic receptors, were conducted in rats trained to discriminate nicotine (0.5 mg/kg s.c.) from saline solution in a two-lever, food-reinforced, operant task. Nicotine administered into the medial prefrontal cortex substituted for nicotine (0.5 mg/kg s.c.), whereas nicotine administered into the nucleus accumbens and ventral tegmental area partially substituted for sc injected nicotine. However, nicotine administered into the dorsal hippocampus and medial habenular nucleus did not substitute for sc injected nicotine. These results suggest that the medial prefrontal cortex is primarily involved in the DS effects of nicotine, whereas the nucleus accumbens and ventral tegmental area are partially involved.