Journal
NEUROPSYCHOPHARMACOLOGY
Volume 27, Issue 5, Pages 723-726Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0893-133X(02)00367-6
Keywords
D2 receptor isoforms; electrophysiology; Parkinson's disease; schizophrenia; substantia nigra; ventral tegmental area
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Two isoforms of the dopamine (DA) D2 receptor are generated from the same gene by alternative splicing, D2L and D2S. To identify which isoform is involved in the autoregulation of midbrain DA neuron activity, intracellular electrophysiological recordings were performed from substantia nigra and ventral tegmental area neurons Of mice lacking either D2L(D2L -/-) or both D2L and D2S receptors mice, DA and quinpirole, a DA D2-like receptor agonist, produced a significant somatic membrane hyperpolarization, which led to a reversible inhibition of firing activity. Interestingly, this effect was fully abolished in D2 -/- neurons but still present in D2L -/- DA neurons. These data clearly show that D2S receptors are the main somatodendritic autoreceptors of central DA neurons. Thus, pharmacological compounds able to interfere selectively with presynaptic D2S receptors might constitute effective therapeutic strategies in neuropsychiatric disorders, by causing negligible side-effects. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
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