Dorsal raphe stimulation differentially modulates dopaminergic neurons in the ventral tegmental area and substantia nigra

The serotoninergic (5-HT) input from the dorsal raphe nucleus (DRN) to midb rain dopamine (DA) neurons is one of the most prominent. In this study, usi ng standard extracellular single cell recording techniques we investigated the effects of electrical stimulation of the DRN on the spontaneous activit y of substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) DA neurons in anesthetized rats. Poststimulus time histograms (PSTH) revea led two different types of response in both SNpc and VTA. Some cells exhibi ted an inhibition-excitation response while in other DA neurons the initial response was an excitation followed by an inhibition. In SNpc, 56% of the DA cells recorded were initially inhibited and 31% of the DA cells were ini tially excited. In contrast, 63% of VTA DA cells were initially excited and 34% were initially inhibited. Depletion of endogenous 5-HT by the neurotox in, 5,7-dihydroxytryptamine (5,7-DHT), and the 5-HT synthesis inhibitor par a-chlorophenylalanine (PCPA), almost completely eliminated the inhibition-e xcitation response in both SNpc and VTA DA cells, without changing the perc entage of DA cells initially excited. Consequently, the proportion of DA ne urons that were not affected by DR stimulation increased after 5-HT depleti on (from 13% to 60% in SNpc and from 6% to 31% in VTA). In several DA cells , DRN stimulation caused important changes in firing rate and firing patter n. These data strongly suggest that the 5-HT input from the DRN is mainly i nhibitory. It also suggests that 5-HT afferences modulate SNpc and VTA DA n eurons in an opposite manner. Our results also suggest that non-5-HT inputs from DR can also modulate mesencephalic DA neurons. A differential modulat ion of VTA and SNpc DA neurons by 5-HT afferences from the DRN could have i mportant implications for the development of drugs to treat schizophrenia o r other neurologic and psychiatric diseases in which DA neurons are involve d. Synapse 35:281-291, 2000. (C) 2000 Wiley-Liss, Inc.