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Feedback Control of Mesolimbic Somatodendritic Dopamine Release in Rat Brain
Author(s) -
Rahman Shafiqur,
McBride William J.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.740684.x
Subject(s) - nomifensine , microdialysis , nucleus accumbens , ventral tegmental area , dopamine , postsynaptic potential , extracellular , autoreceptor , chemistry , sulpiride , neurotransmitter , pharmacology , antagonist , medicine , endocrinology , neuroscience , receptor , biology , dopaminergic , biochemistry
The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dualprobe in vivo microdialysis. Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR‐12909 (10‐1,000 μ M ) or nomifensine (10‐1,000 μ M ) dose‐dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA. Coperfusion of 100 μ M nomifensine with either 100 μ M SCH‐23390 (SCH), a D1 antagonist, or 100 μ M sulpiride (SUL), a D2 receptor antagonist, produced either an additive (for SCH) or a synergistic (for SUL) elevation in the extracellular levels of DA in the ACB, whereas the reduction in the extracellular levels of DA in the VTA produced by nomifensine alone was completely prevented by addition of either antagonist. Application of 100 μ M SCH or SUL alone through the microdialysis probe in the ACB increased the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA remained unchanged. Overall, the results suggest that (a) increasing the synaptic levels of DA in the ACB activates a long‐loop negative feedback pathway to the VTA involving both D1 and D2 postsynaptic receptors and (b) terminal DA release within the ACB is regulated directly by D2 autoreceptors and may be indirectly regulated by D1 receptors, possibly on interneurons and/or through postsynaptic inhibition of the negative feedback loop.