Nicotine and amphetamine acutely cross-potentiate their behavioral and neurochemical responses in female Holtzman rats

Abstract

Psychostimulants are often used in close temporal proximity to nicotine and have been reported to enhance acutely nicotine's desirability in humans. To investigate the acute associations between amphetamine and nicotine, we examined the potentiative interactions between clinically relevant, low doses of these drugs on locomotor activity, and dopamine overflow in the rat. Locomotor activity was measured by telemetry in the home cage environment, and dopamine overflow was evaluated in striatal slice preparations from female Holtzman rats. When administered simultaneously, nicotine and amphetamine produced a predominantly additive effect on locomotor behavior. However amphetamine, when given 2-4 h before nicotine, strongly potentiated nicotine-induced locomotor activity. Correspondingly, nicotine given 1-4 h before amphetamine robustly enhanced amphetamine-stimulated locomotor activity even when the effects of the nicotine pretreatment dissipated. Acute nicotine pretreatment similarly potentiated the effects of dopamine transporter ligands, cocaine, nomifensine, and methamphetamine but not a direct dopamine receptor agonist. Consistent with the behavioral studies, in vivo nicotine pretreatment exaggerated amphetamine-induced dopamine efflux from rat striatal slices. Likewise, in vivo pretreatment of rats with amphetamine potentiated nicotine-induced dopamine efflux from striatal slices. Direct pretreatment of striatal tissue by nicotine also potentiated subsequent amphetamine-stimulated dopamine overflow, further suggesting that the nicotine-amphetamine interaction occurs at the level of the dopamine terminal. Overall, the present data demonstrate that acute interactions of nicotine and other psychomotor stimulants produce potentiative effects and that these transient interactions may play a role in the frequent co-use and abuse of nicotine and other stimulants.