Serotonin (5-HT) is a neurotransmitter that has an essential role in the regulation of emotion but the precise circuits regulating aversive states have not yet been clearly defined. Here the authors “show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRFBNST) in mice. Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT2CRs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus.” The paper also shows that this CRF inhibitory circuit underlies aversive behavior following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin-releasing factor type 1 receptor (CRF1R or CRHR1). The study concludes that there is an essential serotonin→CRF circuit governing fear and anxiety, and provides a potential explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders.
Marcinkiewcz CA, Mazzone CM, D’Agostino G, Halladay LR, Hardaway JA, DiBerto JF, Navarro M, Burnham N, Cristiano C, Dorrier CE, Tipton GJ, Ramakrishnan C, Kozicz T, Deisseroth K, Thiele TE, McElligott ZA, Holmes A, Heisler LK, Kash TL: Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature [Epub ahead of print, Aug. 24, 2016; doi: 10.1038/nature19318].