?Real time? measurement of endogenous dopamine release during short trains of pulses in slices of rat neostriatum and nucleus accumbens : role of autoinhibition

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Abstract
Release of endogenous dopamine elicited in slices of rat neostriatum or nucleus accumbens by a single electric pulse or by trains of 4 or 10 pulses was examined using fast cyclic voltammetry. Single electric pulses gave rise to a marked and transient increase in the extracellular concentration of dopamine in the neostriatum (by 0.43 μmol/l) and nucleus accumbens (by 0.39 μmol/l). The overflow elicited by subsequent pulses delivered at a frequency of 0.2 Hz caused separate but much smaller peaks of dopamine concentration, whereas the overflow elicited by subsequent pulses delivered at 1 Hz caused only a shoulder in the descending limb of the peak due to pulse 1. Four pulses at 5 Hz produced a monophasic response that was higher than the single pulse-evoked peak. Nomifensine 1 μmol/l greatly increased and prolonged the evoked overflow of dopamine. In the absence of nomifensine, metoclopramide 0.3 μmol/l did not change the response to a single pulse or 4 pulses delivered at 0.2 Hz but increased the response to 4 or 10 pulses at 1 Hz and to 4 pulses at 5 Hz. In the presence of nomifensine, metoclopramide increased the response to a single pulse as well as, to a greater extent, the response to 4 pulses at 0.2 Hz and 4 pulses at 1 Hz. Sulpiride 1 μmol/l produced effects similar to those of metoclopramide in the neostriatum in the presence of nomifensine. During trains of pulses at 0.2 or 1 Hz, metoclopramide and sulpiride did not increase (or increased only slightly in the presence of nomifensine) the initial peak that reflected dopamine overflow elicited by pulse 1, but increased greatly the subsequent peaks (0.2 Hz) or the sholder (1 Hz) that reflected the overflow due to the subsequent pulses. The study demonstrates the release of dopamine in the neostriatum and nucleus accumbens with high temporal resolution so that, at least at low frequency, the release elicited by each pulse in a train can be recognized. As previously concluded from experiments with 3H-dopamine, single pulses elicit a large release whereas subsequent pulses delivered at 0.2 to 5 Hz elicit much smaller release. Presynaptic autoinhibition develops immediately after pulse 1 in trains of appropriately spaced pulses. However, it is only partly responsible for the marked fall in release after pulse 1; other, unknown factors contribute to the decline.

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