The mesolimbic system of the brain has been shown to be involved in the reward properties of a number of agents. It is possible that release of monoamines by nicotine in this brain area could be related to the pleasurable aspects related to cigarette smoking. In this investigation, the effect of nicotine on the release of [3H]dopamine in the nucleus accumbens of the rat was studied. It was shown that nicotine produced a concentration-dependent increase in [3H]dopamine release at concentrations of 0.1 microM and above. The increase in release was found to be almost completely calcium dependent. The nicotine-induced release was only partially blocked by the nicotinic antagonists hexamethonium and d-tubocurarine. A number of cholinergic agonists, as well as other compounds, were tested for their capacity to mimic the effect of nicotine. At equimolar concentrations there was, at most, only 50% of the activity of nicotine. The results of this study demonstrate that nicotine stimulates the release of dopamine in the nucleus accumbens at concentrations similar to those in the blood of cigarette smokers. This suggests that the release of monoamines in specific nuclei of the mesolimbic system may be an important determinant of the desire to smoke cigarettes.
After injection of H(3)-norepinephrine into the left lateral cerebral ventricle of cats, the lateral and third cerebral ventricles were perfused with an artificial cerebrospinal fluid. Addition of d-amphetamine to the perfusion fluid caused a significant increase in the concentration of H(3)-norepinephrine in the effluent.
Nicotine was administered acutely and subchronically (14 days) to determine whether various synaptic mechanisms are selectively altered in the nigrostriatal and mesolimbic dopaminergic systems in the rat. When added to tissue preparations in vitro, nicotine had no effects on tyrosine hydroxylase, synaptosomal uptake of [3H]dopamine or binding of [3H]spiperone to D2 receptors in either system. However, acute treatment in vivo stimulated tyrosine hydroxylase activity in the nucleus accumbens. This effect was prevented by pretreatment with a nicotinic antagonist, suggesting that it was mediated by nicotinic receptors. Since subchronic exposure to nicotine had no effect on tyrosine hydroxylase, it appears that tolerance develops to this action. In vivo treatment with nicotine did not alter dopamine uptake or receptor binding. The results suggest that, in doses which result in moderate plasma levels, nicotine has selective stimulant actions on nerve terminals of the mesolimbic system.
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