Serotonin neurons in the median raphe nucleus bidirectionally regulate somatic signs of nicotine withdrawal in mice

Nishitani, Naoya; Ohmura, Yoshiaki; Kobayashi, Keita; Murashita, Taichi; Yoshida, Takayuki; Yoshioka, Mitsuhiro

doi:10.1016/j.bbrc.2021.05.052

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Interestingly, a similar shift in 5-HT 1A receptor function has been observed, also from DRN to MRN, in the psychostimulant responses to chronic cocaine [ 66 ]. In addition, while nicotine-withdrawal following short-term exposure (7 days) recruits DRN 5-HT neurons [ 67 ], it is likely that nicotine-withdrawal following longer exposure (6 weeks) is mostly controlled by MRN 5-HT neuron activity [ 68 ], suggesting that a neuroadaptive shift between DRN and MRN neurotransmission could mediate the transitioning from short-term consumption to long-term substance abuse. However, an opposite shift, from MRN to DRN, has also been demonstrated in the transition from moderate to compulsive cocaine intake following SERT selective knock down in the different raphe nuclei [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice

Belmer

Depoortère²,

Beecher

et al. 2022

Mol Psychiatry

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Alcohol-use-disorders are chronic relapsing illnesses, often co-morbid with anxiety. We have previously shown using the “drinking-in-the-dark” model in mice that the stimulation of the serotonin receptor 1A (5-HT1A) reduces ethanol binge-drinking behaviour and withdrawal-induced anxiety. The 5-HT1A receptor is located either on Raphe neurons as autoreceptors, or on target neurons as heteroreceptors. By combining a pharmacological approach with biased agonists targeting the 5-HT1A auto- or heteroreceptor and a chemogenetic approach (DREADDs), here we identified that ethanol-binge drinking behaviour is dependent on 5-HT1A autoreceptors and 5-HT neuronal function, with a transition from DRN-dependent regulation of short-term (6 weeks) ethanol intake, to MRN-dependent regulation after longer ethanol exposure (12 weeks). We further identified a serotonergic microcircuit (5-HTMRN→DG) originating from the MRN and projecting to the dentate gyrus (DG) of the hippocampus, that is specifically affected by, and modulates long-term ethanol consumption. The present study indicates that targeting Raphe nuclei 5-HT1A autoreceptors with agonists might represent an innovative pharmacotherapeutic strategy to combat alcohol abuse.

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