CHARACTERISTICS OF ELECTRICALLY-EVOKED SOMATODENDRITIC DOPAMINE RELEASE IN SUBSTANTIA-NIGRA AND VENTRAL TEGMENTAL AREA IN-VITRO

Somatodendritic dopamine (DA) release from neurons of the midbrain rep resents a nonclassical form of neuronal signaling. We assessed charact eristics of DA release during electrical stimulation of the substantia nigra pars compacta (SNc) in guinea pig midbrain slices. With the use of parameters optimized for this region, we compared stimulus-induced increases in extracellular DA concentration ([DA](o)) in medial and l ateral SNc, ventral tegmental area (VTA), and dorsal striatum in vitro . DA release was monitored directly with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Detection of DA in SNc was confirmed by electrochemical, pharmacological, and anatomic criteria. Voltammog rams of the released substance had the same peak potentials as those o f DA obtained during in vitro calibration, but different from those of the indoleamine 5-hydroxytryptamine. Similar voltammograms were also obtained in the DA-rich striatum during local electrical stimulation. Contribution from the DA metabolite dihydroxyphenylacetic acid to soma todendritic release was negligible, as indicated by the lack of effect of the monoamine oxidase inhibitor paragyline (20 mu M) on the signal . Lastly, DA voltammograms could only be elicited in regions that were subsequently determined to be positive for tyrosine hydroxylase immun oreactivity (TH-ir). The frequency dependence of stimulated DA release in SNc was determined over a range of 1-50 Hz, with a constant durati on of 10 s. Release was frequency dependent up to 10 Hz, with no furth er increase at higher frequencies. Stimulation at 10 Hz was used in al l subsequent experiments. With this paradigm, DA release in SNc was te trodotoxin insensitive, but strongly Ca2+ dependent. Stimulated [DA](o ) in the midbrain was also site specific. At the midcaudal level exami ned, DA efflux was significantly greater in VTA (1.04 +/- 0.05 mu M, m ean +/- SE) than in medial SNc (0.52 +/- 0.05 mu M), which in turn was higher than in lateral SNc (0.35 +/- 0.03 mu M). This pattern followe d the apparent density of TH-ir, which was also VTA > medial SNc > lat eral SNc. This report has introduced a new paradigm for the study of s omatodendritic DA release. Voltammetric recording with electrodes of 2 -4 mu m tip diameter permitted highly localized, direct detection of e ndogenous DA. The Ca2+ dependence of stimulated release indicated that the process was physiologically relevant. Moreover, the findings that somatodendritic release was frequency dependent across a range charac teristic of DA cell firing rates and that stimulated [DA](o) varied ma rkedly among DA cell body regions have important implications for how dendritically released DA may function in the physiology and pathophys iology of substantia nigra and VTA.