(-)-Nornicotine partially substitutes for (+)-amphetamine in a drug discrimination paradigm in rats

Rats were trained in a two-lever food-reinforced operant task to discriminate (+)-amphetamine (1 mg/kg) from saline. After discrimination training stabilized, test doses of (+)-amphetamine (0.0625-2.0 mg/kg), (-)-nicotine (0.1-1.0 mg/kg), or (-)-nornicotine (1-10 mg/kg) were assessed for their ability to substitute for the (+)-amphetamine training dose during brief test sessions in which food reinforcement was withheld. As expected, as the test dose of (+)-amphetamine increased, there was a dose-related increase in drug-appropriate responding, with both 1 and 2 mg/kg test doses substituting fully for the (+)-amphetamine training dose. Both (-)-nicotine and (-)-nornicotine showed partial substitution (approximately 50% drug-appropriate responding) for the (+)-amphetamine training dose, with (-)-nicotine being more potent than (-)-nornicotine. Rate suppressant effects prevented the assessment of higher doses of (-)-nicotine or (-)-nornicotine. Thus, while (-)-nicotine and (-)-nornicotine share similar discriminative stimulus properties, the mechanism that mediates this effect appears to differ, at least in part, from that activated by (+)-amphetamine.