Work

Reinstatement of escitalopram and clonidine administration reverses the cessation-induced enhanced activation of rat norepinephrine and serotonin neuronal firing activity

Year: 2026

Type: article

Abstract: Background: Abrupt cessation of serotonin (5-HT) reuptake inhibitors (SRIs) in men and women induces a constellation of somatic and psychological symptoms known as discontinuation SRI syndrome; however, the underlying neurophysiological mechanisms remain unclear. Aims: While previous work has largely focused on 5-HT dysregulation, this study assessed whether norepinephrine (NE) signalling may play a critical role. Methods: Using in vivo electrophysiology, the firing activity of locus coeruleus NE and dorsal raphe nucleus 5-HT neurons was examined in male rats following sustained escitalopram administration for 14 days and its subsequent cessation for 2 days to allow its elimination. Results: Escitalopram cessation produced a marked increase in the suppressed firing rate of NE neurons and a doubling of the normalized firing rate of 5-HT neurons. Acute intravenous injection of escitalopram restored the firing rate of both neuronal populations to their prior firing levels after the drug had been administered for 14 days. Acute intravenous injection of the α 2 -adrenoceptor agonist clonidine had the same effect as the re-introduction of escitalopram on both populations of neurons. Conclusions: These results show that abrupt cessation of the SRI escitalopram resulted in robust overactivation of both NE and 5-HT neurons. Normalization of the SRI cessation-induced overactivation of NE and 5-HT neurons by the acute inhibition of the 5-HT reuptake transporter is consistent with the rapid relief of discontinuation symptoms observed in patients resuming their SRI. A similar effect of clonidine on NE and 5-HT neuronal firing would support its use in managing discontinuation symptoms seen after SRI cessation.

Source: Journal of Psychopharmacology

DOI: 10.1177/02698811261478602

Authors: Mostafa El Mansari, Naomichi Okamoto, Pierre Blier

Institutions: Royal Ottawa Mental Health Centre, Institute of Mental Health Research

Language: English

Topic: Neurotransmitter Receptor Influence on Behavior

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,400