Effects of Chronic Nicotine Administration on mRNA Expression of Melanocortin Receptors, Corticotropin-Releasing Factor and Corticotropin-Releasing Factor Receptors In Rat Brain
Project no. 21086 · Status: Kapanmış · 2019
Summary
We aimed to investigate differences in expression of corticotropin-releasing hormone (CRH), CRH receptor and melanocortin (MC) receptor mRNAs in the mesocorticolimbic dopaminergic system during nicotine reward and nicotine withdrawal. Therefore 40 male Wistar rats were divided into four groups: nicotine reward (0W), 24 hours nicotine withdrawal (24W), 48 hours nicotine withdrawal (48W) and control group (n=10). For 12 weeks the control group was only administered tap water and the remaining groups were administered nicotine (during the first week 25 µg / ml; the next 11 weeks 50 µg / ml, free base) dissolved in tap water. In the 13th week control and 0W groups were decapitated immediately. 24W and 48W groups were decapitated 24 and 48 hours after cessation of nicotine administration. MC receptor (MC3R and MC4R), CRH and CRH receptor (CRH-R1 and CRH-R2) mRNA levels were measured by quantitative real-time PCR in ventral tegmental area (VTA), medial hypothalamus (MHA), amygdala (AMG), hippocampus, nucleus accumbens (NAc), dorsal striatum (DST), septum (SEP) ve medial prefrontal cortex (mPFC). One-way ANOVA and post-hoc Tukey tests were performed to demonstrate mRNA expression differences in each brain area. When Tukey test results was not statistically significant, post-hoc Duncan test was performed. CRH mRNA levels in PFC 0W,24W and 48W groups (p<0,001), in SEP of 48W (p<0,05) group and in AMG of 0W group (p=0,005) were significantly higher than the controls. In MHA, CRH mRNA levels in 24W and 48W groups were found significantly higher than 0W group (p<0,05). CRH-R1 mRNA levels in AMG of 0W (p=0,02) and 48W (p=0,023) groups, in NAc of 0W, 24W and 48W groups (p<0,05) and in SEP of 48W group (p=0,045) were increased compared to the control group. CRH-R2 mRNA levels were not statistically significant among groups in any of the brain areas. MC4R mRNA levels; in PFC of 24W (p=0.038) and 48W (p=0.007) groups, in NAc of 0W group(p=0,042), in SEP of 48W group (p=0.03) and in DST 24W group (p=0.022) were significantly increased compared to control group. On the other hand MC3R mRNA levels in MHA of 48W group (p=0,014) and VTA of 24W (p=0,01) and 48W (p=0,003) groups were signficantly increased compared to the control group. The enhancement of CRH, CRH-R1, MC3R and MC4R mRNA levels during chronic nicotine administration and withdrawal may be related to the regulation of negative affective state. Melanocortin and CRH receptors may be alternative molecular targets for the treatment of nicotine addiction.