D-1 DOPAMINE-RECEPTOR STIMULATION INHIBITS FIRING ACTIVITY OF MIDBRAIN DOPAMINE NEURONS IN RESERPINE TREATED RATS - AN EFFECT ELIMINATED AFTER HEMITRANSECTION OF DIENCEPHALON

It has been reported that systemic administration of the D-1 dopamine (DA) receptor agonist SKF 38393 inhibits the firing rate of substantia nigra pars compacta (SNC, A9) DA neurons after repeated reserpine tre atment in locally anesthetized rats, although SKF 38393 induces little effect on the firing of midbrain DA neurons in normal rats. The prese nt study found that local pressure microejection of SKF 38393 (10(-2) M, 20-100 nl) to SNC or substantia nigra pars reticulata (SNR) failed to influence the firing of SNC DA neurons in reserpinized rats (reserp ine 1 mg/kg x 6 days, s.c.); subsequent intravenous (i.v.) injection o f SKF 38393 (4 mg/kg), however, inhibited their firing and the inhibit ion was reversed by the D-1 receptor antagonist SCH 23390. Similarly, systemic administration of SKF 38393 (4 mg/kg, i.v.) inhibited the fir ing of ventral tegmental area (VTA, A10) DA cells in reserpinized rats , while local microejection of SKF 38393 (10(-2) M, 30-60 nl) did not affect their firing. Furthermore, the inhibitory effect of systemic SK F 38393 on firing rate of either SNC or VTA DA neurons in reserpinized rats was eliminated after hemitransection of diencephalon. These resu lts suggest that repeated reserpine treatment renders midbrain DA neur ons responsive to D-1 receptor stimulation and that D, receptor agonis t-induced inhibition of midbrain DA cell firing in reserpinized rats m ay require the involvement of long-loop feedback pathways. (C) 1996 Wi ley-Liss, Inc.