Stimulation of nigrostriatal dopamine neurones by nicotine.

In rats anaesthetized with urethane, firing of neurones of the substantia nigra zona compacta was accelerated after subcutaneous or iontophoretic administration of nicotine or after iontophoretic application of acetylcholine. The excitation was prevented by iontophoretic application of dihydro-beta-erythroidine, but not by atropine. The units were identified by antidromic stimulation as neurones of the nigrostriatal system; their activity was depressed by iontophoretically applied dopamine (DA). Under the same conditions of anaesthesia, a subcutaneous injection of nicotine produced an increase in DA turnover and in homovanillic acid levels in the striatum. The effect of nicotine on striatal DA turnover was comparable to that of electrical stimulation of the nigrostriatal pathway at the average frequency seen in the firing of zona compacta neurones after systemic administration of nicotine. These observations corroborate the idea that nicotine exerts an excitatory action at the level of nigral DA nerve cells. Observations made after electrical stimulation or haloperidol under urethane anaesthesia and after nicotine in unanaesthetized rats suggest that the relatively modest effect of nicotine on striatal DA turnover is due mainly to the short duration of drug action rather than to effects of the anaesthetic on DA metabolism.