Nicotinic effects on the firing pattern of midbrain dopamine neurons

The effects of systemic administration of nicotine or the nicotinic antagonist mecamylamine on the midbrain dopamine (DA) systems of the rat were studied with single cell recording techniques. Dopamine cells of the zona compacta, substantia nigra (ZC-SN) and the ventral tegmental area (VTA) were identified by their characteristic action potentials, antidromic stimulation methodology and conventional histological procedures. Firing rates as well as firing patterns were determined from computer-generated interspike interval histograms describing burst-firing in relation to single-spike firing. A larger proportion of burst-firing DA cells was found in the VTA when compared with the ZC-SN area. (-)-Nicotine bitartrate (0.5 mg kg-1 i.p.) not only increased the firing rate of ZC-SN neurons but also the amount of burst firing of the ZC-SN neurons and VTA neurons, respectively. Mecamylamine HCl (4.0 mg kg-1 i.p.) decreased the firing rate of VTA cells which, in principle, indicates a tonic nicotinic input in this area. The increase in firing rate of central DA neurons following nicotine administration was found to be associated with increased bursting of the burst firing cells whereas, in contrast, the non-bursting neurons did not respond with burst-firing. Generally, the correlation between nicotine induced changes in firing rate and in burst-firing activity, respectively, was found to be low for midbrain DA neurons. These observations, in conjunction with the previous demonstration of nicotinic receptors in these areas, indicate the existence of a nicotinic input, specifically regulating the firing pattern of these central DA cells. This neuromodulatory effect of nicotine may be significant for its behavioural stimulant action.(ABSTRACT TRUNCATED AT 250 WORDS)