Interaction of nicotine with dopaminergic mechanisms assessed through drug discrimination and rotational behaviour in rats

Biochemical and electrophysiological studies have suggested that nicotine may interact with dopaminergic systems so as to enhance the release and utilization of dopamine. The functional significance of these effects has been assessed using drug discrimination and rotational behaviour in rats. The dopamine antagonists haloperidol and Sch 23390 attenuated the discriminative stimulus effect of nicotine and reduced overall rates of responding. In contrast, droperidol and pimozide were without significant effect on discrimination of nicotine at doses that reduced response rates. There was partial generalization from nicotine to the dopamine D-1 agonist SKF 38393. In rats with unilateral, 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, nicotine produced rotation towards the side of the lesion, a characteristic effect of indirectly acting dopamine agonists such as amphetamine. The nico tinic-cholinergic antagonist mecamylamine, and haloperidol, blocked rotation produced by nicotine. A dose of nicotine that was too small to produce amphetamine-like effects itself enhanced both the discriminative stimulus and the rotational behaviour produced by amphetamine. However, mecamylamine did not weaken the discriminative effect of amphetamine. The results suggest that there may be a minor component of the nicotine discriminative stimulus that is mediated, indirectly, through a dopaminergic mechanism. There also appears to be a facilitatory, nicotinic influence on behavioural functions linked to the dopamine system.