title: Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions.
abstract: Our previous genetic studies demonstrated that variants of the gamma-Aminobutyric acid B receptor subunit 2 (GPR51) and neurotrophic tyrosine kinase receptor type 2 (NTRK2) genes are significantly associated with nicotine dependence (ND) in smokers. However, whether such genetic associations lead to changes in the expression of the two genes in response to nicotine remains undetermined. In this study, we investigated the regulatory effect of nicotine on the expression of Gpr51 and Ntrk2 in seven rat brain regions during the administration of nicotine in a daily dose of 3.15 mg/kg for 7 days. With quantitative real-time RT-PCR, we found that nicotine increased the mRNA of Gpr51 by 70, 78, and 32% in the amygdala, striatum, and prefrontal cortex (PFC), respectively, but decreased by 54% in the nucleus accumbens (NA). The Gpr51 protein was upregulated by nicotine in the amygdala (26%), striatum (73%), PFC (28%), and medial basal hypothalamus (MBH; 19%) but downregulated in the NA (-72%). Similarly, the mRNA level of Ntrk2 was enhanced by nicotine in the striatum (86%) and PFC (38%), but decreased in the NA (-46%) and ventral tegmental area (VTA; -49%). A significant change in protein expression was also obtained for Ntrk2 in the PFC (24%), MBH (33%), NA (-33%), and VTA (-70%). Interestingly, these two genes showed a closely coordinated expression pattern in response to nicotine in most of the brain regions examined. In summary, our results demonstrate that the expression of Gpr51 and Ntrk2 is significantly regulated by nicotine at both the mRNA and protein levels in various brain regions, which provides further evidence that these two genes are involved in the etiology of ND, as reported in our previous genetic association studies in humans.
authors.affiliation: Section of Neurobiology, Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA 22911, USA.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Sun
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
authors.forename: Yoon Y
authors.initials: YY
authors.lastname: Hwang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C116566:Gabbr2 protein, rat; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D009538:Nicotine; D020813:Receptor, trkB