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

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 mumol/l) and nucleus accumbens (by 0.39 mumol/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 mumol/l greatly increased and prolonged the evoked overflow of dopamine. In the absence of nomifensine, metoclopramide 0.3 mumol/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 mumol/l produced effects similar to those of metoclopramide in the neostriatum in the presence of nomifensine.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

“…Consistent with previous data Bull and Sheehan, 1991;Limberger et al, 1991;Trout and Kruk, 1992;Garris et al, 1994), evoked DA release in C Pu and NAc was regulated strongly by D 2 autoreceptor inhibition, as indicated by the marked enhancement of [DA] o after D 2 receptor antagonism by sulpiride and the reduction of [DA] o during D 2 agonism by quinpirole. The time course of autoinhibition in C Pu was consistent with a time delay for D 2 receptor activation by DA in vitro.…”

“…DA was detected with FCV at a carbon fiber microelectrode after electrical stimulation in SNc, VTA, CPu, or nucleus accumbens (NAc), as described previously Palij et al, 1990;Limberger et al, 1991;Trout and Kruk, 1992;Iravani et al, 1996;Cragg et al, 1997;Rice et al, 1997), with either multisecond stimulation trains (30 -40 pulses at 10 Hz) or a pseudo-one pulse stimulation (10 pulses at 100 Hz). The identification of extracellular signals evoked by 10 Hz stimulation as DA and not other monoamines or metabolites was confirmed previously Rice et al, 1997) on the basis of anatomical, electrochemical (see also Figs.…”

“…Defining these factors in SNc and VTA will be a vital step in understanding fundamental features of somatodendritic signaling in these key regions. There are two mechanisms that are central in the control of axon terminal DA neurotransmission in striatum in addition to DA synthesis and the initial response to depolarization: DA uptake via the DA transporter (DAT) Cass et al, 1992;Kawagoe et al, 1992;Nicholson, 1995;Giros et al, 1996) and inhibition of release via presynaptic D 2 -like autoreceptors Bull and Sheehan, 1991;Limberger et al, 1991;Trout and Kruk, 1992;Garris et al, 1994). In contrast, DA uptake in somatodendritic regions is markedly less avid Simon and Ghetti, 1993;Cragg et al, 1997).…”

Differential action of (+)‐amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens

“…Applying a range of anatomical, electrochemical and pharmacological criteria, it has previously been shown that the voltammetric signal, as measured in this study, following electrical stimulation in striatal brain slices can be attributed to a transient increase in extracellular dopamine concentration Bull et al, 1990;Patel et al, 1992;. By use of fast cyclic voltammetry it is possible to measure dopamine overflow evoked by a wide range of electrical stimuli, ranging from a single pulse to long trains applied over a wide range of frequencies with a time resolution which approaches real time Limberger et al, 1991;.…”

Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release

“…In the neostriatum and nucleus accumbens, dopamine autoinhibition is mediated via dopamine D2-like receptors (Dugast et al, 1997). Although other in vitro studies have demonstrated that activation of release-regulating autoreceptors by short trains of pulses occurs over a time frame of approximately 1 sec (Limberger et al, 1991;Kennedy et al, 1992), the explicit timecourse of action of these autoreceptors on subsequent dopamine release has not been previously determined. Yet the window of such autoinhibition (onset, magnitude, and duration) clearly has important implications for the local control of extracellular dopamine in the forebrain.…”