Coupled intracerebral microdialysis and electrophysiology for the assessment of dopamine neuron function in vivo

Introduction: The central dopaminergic system is involved in the pathophysiology of several neuropsychiatric disorders. Intracerebral microdialysis and electrophysiology provide two powerful techniques to investigate dopamine (DA) function and the mechanism of action of psychotropic drugs in vivo. Methods: Here, we developed a protocol allowing the combined measurement of neurochemical and electrical activities of the nigrostriatal and mesoaccumbens DA pathways, by coupling in vivo microdialysis and electrophysiology in the same isoflurane-anesthetized animal. DA neuron firing rate and burst firing were measured in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), whereas extracellular levels of DA and its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were monitored in the striatum and the nucleus accumbens (NAc). The validity of the protocol was assessed using various drugs known to modify DA neuron activity in vivo. Results: The peripheral administration of the DA-D2 agonist quinpirole decreased SNc DA neuron firing rate and burst firing, as well as DA and DOPAC outflow in the rat striatum. Opposite effects were observed after the peripheral administration of the DA-D2 antagonist haloperidol. In rats and mice, the peripheral administration of cocaine elicited a decrease in VTA DA neuron firing rate and burst firing, and an increase in accumbal DA outflow, paralleled by a reduction in DOPAC outflow. Discussion: The obtained results, confirming previous electrophysiological and microdialysis studies, demonstrate that this protocol provides a suitable method for the study of DA neuron function and the mechanism of action of psychotropic drugs in the living brain of both rats and mice.