Nitric Oxide Modulation of the Dopaminergic Nigrostriatal System: Focus on Nicotine Action

Abstract

Nitric oxide (NO) signalling plays an important role in the integration of information processed by the basal ganglia nuclei. Accordingly, considerable evidence has emerged indicating a role for NO in pathophysiological conditions such as Parkinson's disease (PD), schizophrenia and drug addiction. To further investigate the NO modulation of dopaminergic function in the basal ganglia circuitry, in this study we used in vivo electrophysiology and microdialysis in freely-moving rats. Pharmacological manipulation of the NO system did not cause any significant changes either in the basal firing rate and bursting activity of the dopamine (DA) neurons in the substantia nigra pars compacta (SNc) or in DA release in the striatum. In contrast, the disruption of endogenous NO tone was able to counteract the phasic dopaminergic activation induced by nicotine treatment in both experimental approaches. These results further support the possibility that nicotine acts via a NO mechanism and suggest a possible state-dependent facilitatory control of NO on the nigrostriatal DA pathway. Thus, NO selectively modulates the DA exocytosis associated with increased DA function.