Interaction of lobeline and nicotinic receptor ligands with the discriminative stimulus properties of cocaine and amphetamine

Lobeline has high affinity for nicotinic acetylcholine receptors and inhibits the function of vesicular and plasmalemmal monoamine transporters. Moreover, lobeline has been shown to alter the neurochemical and behavioral effects of psychostimulants. The present study determined the effect of lobeline and drugs selective for nicotinic receptors on the discriminative stimulus properties of low doses of cocaine (1.6 or 5.0 mg/kg) or d-amphetamine (0.3 mg/kg) in rats, using a standard two-lever drug discrimination procedure with food reinforcement. Nicotine substituted for both amphetamine and cocaine. The nicotinic receptor antagonists mecamylamine and hexamethonium did not substitute for or block the cocaine or amphetamine stimulus. In contrast, lobeline substituted for cocaine, but did not substitute for amphetamine. In antagonism tests, lobeline doses that did not substitute for cocaine decreased responding on the cocaine-paired levers. Surprisingly, lobeline did not alter the discriminative stimulus properties of amphetamine. This research further supports the supposition that nicotine, cocaine and amphetamine produce similar, but distinct subjective states. Furthermore, the present findings suggest that lobeline has a complex mechanism of action to disrupt the behavioral effects of drugs of abuse.