Voltammetry as a tool for monitoring dopamine regulation in the striatum: In vivo and in vitro studies

Disturbances in dopamine neurotransmission in the striatal region of the brain have been implicated in schizophrenia, Parkinson's disease, and drug abuse. The goal of this research was to identify endogenous regulatory mechanisms responsible for the control of dopamine release and for the maintenance of the resting extracellular dopamine concentration in this region. Fast scan cyclic voltammetry in conjunction with carbon fiber microelectrodes was the experimental approach applied to probe changes in extracellular levels of dopamine in the brain. The combined voltammetry and microelectrode methodology permits the observation of the important neurotransmission events, neurotransmitter release and re-uptake, and therefore is an attractive technique for studying the regulation of dopamine in discrete brain regions.; The local regulation of dopamine in the striatum by other neurotransmitters was studied in brain slices, a preparation that excludes the input from extra-striatal feedback pathways. These experiments revealed that gamma-aminobutyric acid (GABA) and dynorphins participate in the local regulation of striatal dopamine release. Application of either GABA or kappa-opioid (dynorphin) receptor selective agonists to the slice perfusion medium attenuated dopamine release evoked by focal electrical stimulation of the striatal region of the brain slices. Local striatal infusion or systemic injection of kappa-opioid agonists also inhibited dopamine release evoked by electrical stimulation of nigrostriatal dopamine neurons in anesthetized rats. These results suggest that GABA and dynorphin, through activation of their endogenous receptors, exert an inhibitory input on dopamine release in this region of the brain.; Experiments probing the effects of acute cocaine administration on resting dopamine levels in the striatum demonstrated that cocaine does not cause dramatic increases in the extracellular dopamine concentration as previously hypothesized. Rather, the regulatory input of D2 type dopamine autoreceptors prevents such an increase. Carbon fiber microelectrodes were positioned in the striatum of unanesthetized rats. Systemic injection of cocaine or nomifensine, inhibitors of the dopamine transporter, did not induce changes in the extracellular dopamine concentration in the striatum unless the animal was pretreated with a D2 receptor antagonist. Taken together, these in vitro and in vivo results provide valuable information about the mechanisms responsible for regulation of striatal dopamine levels.