Figure 10: Proposed mechanisms of dopamine-mediated serotonin release.

The substantia nigra (SN) sends dense dopaminergic projections to the striatum (nigrostriatal pathway) and to the dorsal raphe nucleus (DRN).¹ The DRN sends serotonergic projections to dopaminergic cell bodies in the SN and to the striatum.² We found that dopamine-induced serotonin release was not blocked by local D1- or D2-like receptor inhibition in the striatum. Another possible mechanism for dopamine-mediated serotonin release is that an optogenetically induced increase in dopamine in the SN, which promotes D2 somatodendritic autoreceptor activation³ and subsequent disinhibition of serotonin cell bodies in the DRN, produces serotonin release in the striatum. Alternately, optically induced dopamine release in DRN could act via local D1 or D2-like receptors to increase the probability of firing of DRN serotonin neurons projecting to dSTR.