(-)-NORNICOTINE PARTIALLY SUBSTITUTES FOR (-AMPHETAMINE IN A DRUG DISCRIMINATION PARADIGM IN RATS())

Rats were trained in a two-lever food reinforced operant task to discr iminate (+)-amphetamine (1 mg/kg) from saline. After discrimination tr aining 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 asse ssed for their ability to substitute for the (+)-amphetamine training dose during brief test sessions in which food reinforcement was withhe ld. 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 tr aining dose. Both (-)-nicotine and (-)-nornicotine showed partial subs titution (approximately 50% drug appropriate responding) for the (+)-a mphetamine training dose, with (-)-nicotine being more potent than (-) -nornicotine. Rate suppressant effects prevented the assessment of hig her 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 i n part, from that activated by (+)-amphetamine. (C) 1997 Elsevier Scie nce Inc.