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Open AccessArticle

Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures

1
Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064 Ozzano dell’Emilia, Italy
2
Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD2080 Msida, Malta
3
Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
4
Laboratory of Behavioral Physiology, Human Physiology Section “Giuseppe Pagano”, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
5
Unité Mixte de Recherche 5287, Centre National de la Recherche Scientifique, 146 rue Léo Saignat, B.P.281, CEDEX, F-33000 Bordeaux, France
6
School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Eiko Nakamaru-Ogiso
Int. J. Mol. Sci. 2021, 22(9), 4775; https://doi.org/10.3390/ijms22094775
Received: 1 April 2021 / Revised: 25 April 2021 / Accepted: 27 April 2021 / Published: 30 April 2021
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. View Full-Text
Keywords: Ro 60-0175; nucleus accumbens; dorsal raphe nucleus; addiction; depression; medial prefrontal cortex; dentate gyrus; striatum; ventral tegmental area; substantia nigra pars compacta; single cell-extracellular recording Ro 60-0175; nucleus accumbens; dorsal raphe nucleus; addiction; depression; medial prefrontal cortex; dentate gyrus; striatum; ventral tegmental area; substantia nigra pars compacta; single cell-extracellular recording
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MDPI and ACS Style

Bombardi, C.; Delicata, F.; Tagliavia, C.; Grandis, A.; Pierucci, M.; Marino Gammazza, A.; Casarrubea, M.; De Deurwaerdère, P.; Di Giovanni, G. Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures. Int. J. Mol. Sci. 2021, 22, 4775. https://doi.org/10.3390/ijms22094775

AMA Style

Bombardi C, Delicata F, Tagliavia C, Grandis A, Pierucci M, Marino Gammazza A, Casarrubea M, De Deurwaerdère P, Di Giovanni G. Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures. International Journal of Molecular Sciences. 2021; 22(9):4775. https://doi.org/10.3390/ijms22094775

Chicago/Turabian Style

Bombardi, Cristiano; Delicata, Francis; Tagliavia, Claudio; Grandis, Annamaria; Pierucci, Massimo; Marino Gammazza, Antonella; Casarrubea, Maurizio; De Deurwaerdère, Philippe; Di Giovanni, Giuseppe. 2021. "Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures" Int. J. Mol. Sci. 22, no. 9: 4775. https://doi.org/10.3390/ijms22094775

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