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Discovering the mechanisms underlying serotonin (5‐ HT ) 2A and 5‐ HT 2C receptor regulation following nicotine withdrawal in rats
Author(s) -
Zaniewska Magdalena,
Alenitalia,
Wydra Karolina,
Fröhler Sebastian,
Kuśmider Maciej,
McCreary Andrew C.,
Chen Wei,
Bader Michael,
Filip Małgorzata
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13192
Subject(s) - ventral tegmental area , nucleus accumbens , dentate gyrus , nicotine , 5 ht2c receptor , medicine , 5 ht receptor , receptor , endocrinology , serotonin , hippocampus , chemistry , neuroscience , biology , dopaminergic , dopamine
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‐ HT 2A/2C receptors were analyzed on day 3 of nicotine withdrawal. Nicotine withdrawal increased [ 3 H]ketanserin binding to 5‐ HT 2A 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‐ HT 2C receptors was seen in the ventral dentate gyrus. Profound decrease in the 5‐ HT 2A receptor transcript level was noted in the hippocampus and ventral tegmental area. Out of five 5‐ HT 2C 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‐ HT 2C receptor transcript was seen. These results show that the reduction in the 5‐ HT 2A 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‐ HT 2C 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labeling in the hippocampus.Serotonin (5‐HT) 2A/2C receptor ligands alleviate depression‐like state in nicotine‐withdrawn rats.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‐HT 2A 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‐HT 2C receptor mRNA editing in the hippocampus might explain reduced inverse agonist binding to 5‐HT 2C receptor and suggest a shift toward a population of more active receptors. 5‐HT, serotonin; 5‐HT 2A R, 5‐HT 2A receptor; 5‐HT 2C R, 5‐HT 2C receptor.