In vivo voltammetric evidence that cerebral nitric oxide (NO) is influenced by drugs of abuse: is NO implicated in their neurotoxicity?

Abstract

Nitric oxide (NO) has been implicated in mechanisms of neurotoxicity as well as in drug abuse and dependence. Here we analyse the involvement of central NO in the presence of drugs of abuse and in particular to assess the effect of amphetamine (AMPH) and that of ethanol (EtOH) in this system monitored in vivo in the striatum of anaesthetised rats. A voltammetric (electrochemical) methodology able to directly measure real time NO was implemented using specifically treated micro-biosensors and applied. In vitro experiments confirmed the chemical nature of the voltammetric signal monitored at +550 mV, as related to the oxidation of exogenous NO. In vivo experiments in the rat striatum indicated that the amperometric current level is related to the oxidation of endogenous NO. Furthermore, a significant outcome of AMPH and that of ETOH on the NO system monitored in vivo in the striatum of anaesthetised rats was monitored, supporting the implication of the cerebral NO system in the influence of drugs of abuse.