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Discovering the mechanisms underlying serotonin (5-HT)2A and 5-HT2C receptor regulation following nicotine withdrawal in rats

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Item Type:Article
Title:Discovering the mechanisms underlying serotonin (5-HT)2A and 5-HT2C receptor regulation following nicotine withdrawal in rats
Creators Name:Zaniewska, M. and Alenina, N. and Wydra, K. and Fröhler, S. and Kuśmider, M. and McCreary, A.C. and Chen, W. and Bader, M. and Filip, M.
Abstract:We have previously demonstrated that nicotine withdrawal produces depression-like behavior and that serotonin (5-HT)2A/2C receptor ligands modulate that mood-like state. In the present study we aimed to identify the mechanisms (changes in radioligand binding, transcription or RNA-editing) related to such a behavioral outcome. Rats received vehicle or nicotine (0.4 mg/kg, s.c.) for 5 days in home cages. Brain 5-HT2A/2C receptors were analyzed on day 3 of nicotine withdrawal. Nicotine withdrawal increased [(3) H]ketanserin binding to 5-HT2A receptors in the ventral tegmental area and ventral dentate gyrus, yet decreased binding in the nucleus accumbens shell. Reduction in [(3) H]mesulergine binding to 5-HT2C receptors was seen in the ventral dentate gyrus. Profound decrease in the 5-HT2A receptor transcript level was noted in the hippocampus and ventral tegmental area. Out of five 5-HT2C receptor mRNA editing sites, deep sequencing data showed a reduction in editing at the E site and a trend toward reduction at the C site in the hippocampus. In the ventral tegmental area, a reduction for the frequency of CD 5-HT2C receptor transcript was seen. These results show that the reduction in the 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor density in the hippocampus and ventral tegmental area during nicotine withdrawal, while decreased 5-HT2C receptor mRNA editing may explain the reduction in receptor labeling in the hippocampus. Serotonin (5-HT)2A/2C receptor ligands alleviate depression-like state in nicotine-withdrawn rats. Here, we show that the reduction in 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor number in the hippocampus and ventral tegmental area during nicotine withdrawal, while attenuated 5-HT2C receptor mRNA editing in the hippocampus might explain reduced inverse agonist binding to 5-HT2C receptor and suggest a shift toward a population of more active receptors. 5-HT, serotonin; 5-HT2A R, 5-HT2A receptor; 5-HT2C R, 5-HT2C receptor.
Keywords:5-HT2A/2C Receptor Aautoradiography, Deep Sequencing, Nicotine Withdrawal, Real Time PCR, Animals, Rats
Source:Journal of Neurochemistry
ISSN:0022-3042
Publisher:Wiley-Blackwell (U.K.)
Volume:134
Number:4
Page Range:704-716
Date:August 2015
Official Publication:https://doi.org/10.1111/jnc.13192
PubMed:View item in PubMed

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