To investigate the role of D 1 -like receptors in endogenous dopamine (DA)-mediated feedback control of DA neurons in vivo, single unit recordings were made from rat nigral DA cells using low cerveau isole Β΄preparations. The D 2 antagonist raclopride, but not the D 1 antagonist SCH23390, increased baseline activity of DA neurons, suggesting that spontaneously released DA acts primarily through D 2 -like receptors to inhibit DA cells. However, feedback 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 other hand, was always completely reversed by raclopride, suggesting that the D 1 -mediated portion of the inhibition depends upon co-activation of D 2 -like receptors. In rats with forebrain hemitransections, D-amphetamine-induced inhibition was markedly decreased and the remaining inhibition was not blocked by SCH23390, supporting the suggestion that D 1 -D 2 co-activation-induced inhibition is mediated through long feedback pathways. In chloral hydrate-anesthetized rats, D-amphetamine- induced inhibition was also insensitive to SCH23390; however, the degree of the inhibition was not reduced. Combined with previous studies, these data suggest that chloral hydrate not only inactivates the D 1 feedback pathway but also enables the D 2 feedback pathway to operate independently of D 1 -like receptors. Conversely, in parkinsonian animals D 1 receptor activation alone has been reported to inhibit DA cells. Taken together, these results suggest that a major portion of endogenous 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 under certain conditions and may play a role in the pathophysiology of Parkinson's disease.