Nicotine regulates 5-HT(1A) receptor gene expression in the cerebral cortex and dorsal hippocampus.
The 5-HT(1A) receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5-HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute and chronic systemic (--)-nicotine administration on 5-HT(1A) receptor gene expression were measured by in situ hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum. In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the expression of 5-HT(1A) receptor mRNA 2 h and 24 h after injection. Similarly, acute nicotine significantly increased 5-HT(1A) receptor mRNA in the dentate gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after injection. Acute nicotine was without effect in the lateral septum. Chronic nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5-HT(1A) receptor mRNA in the cortex 2 h after the final injection, but was without effect at 24 h or 72 h. Chronic nicotine caused no changes in 5-HT(1A) mRNA in the lateral septum or dorsal hippocampus. These data demonstrate that nicotine regulates 5-HT(1A) receptor gene expression in the cortex and hippocampus. The rapid regulation of expression of 5-HT(1A) receptor mRNA leads to the hypothesis that nicotine-induced 5-HT release may alter the postsynaptic sensitivity to 5-HT.
Kenny
P J
PJ
Psychopharmacology Research Unit, Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, London SE1 1UL, UK.
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Rattray
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D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D018891:Dentate Gyrus / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D013997:Time Factors; D014018:Tissue Distribution
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D009538:Nicotine