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Lateral habenula 5-HT2C receptor function Is altered by acute and chronic nicotine exposures

Bombardi, Cristiano, Delicata, Francis, Tagliavia, Claudio, Grandis, Annamaria, Pierucci, Massimo, Marino Gammazza, Antonella, Casarrubea, Maurizio, De Deurwaerdère, Philippe and Di Giovanni, Giuseppe 2021. Lateral habenula 5-HT2C receptor function Is altered by acute and chronic nicotine exposures. International Journal of Molecular Sciences 22 (9) , 4775. 10.3390/ijms22094775

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Abstract

Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5–640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR) area while decreasing the number of 5-HT2CR-IR neurons in the LHb. On the other hand, chronic nicotine increased both the 5-HT2CR-IR area and 5-HT2CR-IR LHb neurons in the LHb. Western blot analysis confirmed these findings and further revealed an increase of 5-HT2CR expression in the medial prefrontal cortex after chronic nicotine exposure not detected by the immunohistochemistry. Altogether, these data show that acute and chronic nicotine exposure differentially affect the central 5-HT2CR function mainly in the LHb and this may be relevant in nicotine addiction and its treatment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: MDPI
ISSN: 1422-0067
Date of First Compliant Deposit: 2 August 2021
Date of Acceptance: 27 April 2021
Last Modified: 10 Aug 2021 13:30
URI: https://orca.cardiff.ac.uk/id/eprint/143096

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