Endogenous DA-mediated feedback inhibition of DA neurons: Involvement of both D-1- and D-2-like receptors

Wx. Shi et al., Endogenous DA-mediated feedback inhibition of DA neurons: Involvement of both D-1- and D-2-like receptors, SYNAPSE, 35(2), 2000, pp. 111-119
Citations number
Categorie Soggetti
Neurosciences & Behavoir
Journal title
ISSN journal
0887-4476 → ACNP
Year of publication
111 - 119
SICI code
To investigate the role of D-1-like receptors in endogenous dopamine (DA)-m ediated feedback control of DA neurons in vivo, single unit recordings were made from rat nigral DA cells using low cerveau isole preparations. The D- 2 antagonist raclopride, but not the D-1 antagonist SCH23390, increased bas eline activity of DA neurons, suggesting that spontaneously released DA act s primarily through D-2-like receptors to inhibit DA cells. However, feedba ck inhibition induced by an increased DA release by D-amphetamine (1 mg/kg, i.v.) was partially reversed by SCH23390. The same inhibition, on the othe r hand, was always completely reversed by raclopride, suggesting that the D -1-mediated portion of the inhibition depends upon co-activation of D-2-lik e receptors. In rats with forebrain hemitransections, D-amphetamine-induced inhibition was markedly decreased and the remaining inhibition was not blo cked by SCH23390, supporting the suggestion that D-1-D-2 co-activation-indu ced inhibition is mediated through long feedback pathways. In chloral hydra te-anesthetized rats, D-amphetamine-induced inhibition was also insensitive to SCH23390; however, the degree of the inhibition was not reduced. Combin ed with previous studies, these data suggest that chloral hydrate not only inactivates the D-1 feedback pathway but also enables the D-2 feedback path way to operate independently of D-1-like receptors. Conversely, in parkinso nian animals D-1 receptor activation alone has been reported to inhibit DA cells. Taken together, these results suggest that a major portion of endoge nous DA-mediated feedback inhibition is due to concurrent activation of D-1 - and D-2-like receptors. However, this D-1-D-2 interdependence may alter u nder certain conditions and may play a role in the pathophysiology of Parki nson's disease. (C) 2000 Wiley-Liss, Inc.