DIRECT MONITORING OF DOPAMINE AND 5-HT RELEASE IN SUBSTANTIA-NIGRA AND VENTRAL TEGMENTAL AREA IN-VITRO

Fast-scan cyclic voltammetry with carbon fibre microelectrodes was use d to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) re lease from three distinct regions of guinea-pig mid-brain in vitro: ro stral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous electrophysiological studies have demonstrated that ce lls of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase- positive neurons and determined, using high-performance liquid chromat ography, that DA levels were similar in rostral and caudal SN, but low er in SN than in VTA. In each region, application of veratrine, which was shown by intracellular recordings to have a reversible depolarisin g action, evoked a signal attributable to DA and distinguishable from that of 5-HT. Release signals were monitored every 250 ms with a spati al resolution of less than 50 mu m. DA release was calcium-dependent a nd was not detectable in a catecholamine-poor area such as the cerebel lum, or in mid-brain tissue pre-treated with reserpine. Within the nor mal mid-brain, the amount of DA released was correlated with tissue co ntent in that it was higher in the VTA than in either region of SN. It is concluded that DA released from somato-dendritic parts of mid-brai n neurons exhibits site-specific variation. This is the first report o f direct monitoring of DA and 5-HT relase from these regions with in s itu electrodes and demonstrates the utility of fast-scan cyclic voltam metry to investigate the mechanisms and possible non-classical functio ns of somato-dendritic DA release.