Differences In The Expression Of Dopamine Receptor And Dopamine Transporter mRNAs In The Brains Of Nicotine-Preferring Rats

Project no. 29642 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

AIM: The addictive effect of nicotine is closely associated with the activation of dopaminergic neurons in the mesocorticolimbic system, the brain's reward system. This system includes brain regions such as the ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC) and plays critical roles in the regulation of reward, motivation and addiction processes. Addictive substances such as nicotine increase dopamine release in these pathways, triggering reward mechanisms and reinforcing addictive behaviors. The aim of this study was to examine the effects of 5-week chronic nicotine exposure on dopamine D1, D2 and D3 receptors and dopamine transporter protein (DAT) mRNA expressions in the mesocorticolimbic dopamine system of rats. In the study, rats with genetic predisposition to nicotine addiction and control groups were compared to investigate how genetic factors shape addiction processes and the changes that occur in the dopaminergic system in this process. METHOD: 4 groups of adult male animals were formed. 16 animals in the control group receiving water (SC), 10 animals in the nicotine-preferring lines group receiving water (SN), 10 animals in the control group receiving nicotine (NC), and 10 animals in the nicotine-preferring lineage group receiving oral nicotine (NN) received oral nicotine for 5 weeks in a two-bottle free choice paradigm. Nicotine administration was 10 mg/L (free base) for the first 2 weeks and 20 mg/l (free base) for the remaining 3 weeks. After 5 weeks of nicotine intake, dopamine D1, D2, D3 receptors and DAT mRNA expression in NAc, VTA and PFC were measured by real-time PCR. Statistical analyses were performed with ANOVA test to evaluate whether there was a significant difference between the groups. For significant results, p<0.05 level was accepted and comparisons between groups were performed by post-hoc Tukey test. RESULTS: Nicotine-preffering rat lines consumed (p<0.001) and preferred (p=0.031) more nicotine than controls throughout the 5-week nicotine intake. Especially at weeks 4 and 5, nicotine-preffered lines consumed more nicotine than controls (p<0.001) and showed a higher nicotine preference (p<0.001). DRD1 (p=0.014) and DRD2 (p=0.006) mRNA expression in the NAc and DRD3 (p<0.001) and DAT (p=0.007) mRNA expression in the VTA were decreased in nicotine animals compared to water animals. DRD3 (p=0.008) and DAT (p=0.002) mRNA expression in the VTA of nicotine preffered rat lines decreased compared to control animals. In particular, DRD1 (p=0.036) and DRD2 (p=0.042) mRNA expression was decreased in the NAc of the NN group compared to the SN group. Compared to SC, SN and NC groups had decreased DRD3 (for SN: p=0.026; for NC: p=0.002) and DAT (for SN: p=0.01; for NC: p=0.03) mRNA expression in the VTA. CONCLUSION: Nicotine-preferring animals showed marked changes in the mRNA expression of dopamine receptors and dopamine transporter compared to controls. Long-term nicotine exposure resulted in decreased DRD1 and DRD2 receptor mRNA expression in the NAc region of nicotine-preffering animals, whereas no change was observed in controls. The decrease in mRNA expression of DRD1 and DRD2 receptors was associated with down-regulation of the receptors. This may result in decreased dopaminergic transmission. The decreased expression of DRD3 receptor and DAT mRNA expression in the VTA under basal conditions in nicotine-preffering animals may indicate the presence of a hypodopaminergic state in these animals. Nicotine-preffering animals may have a tendency to consume more nicotine to feel better. These results support dysregulation of the dopaminergic system, which has been associated with the development of addiction in the literature, and may increase the propensity for nicotine addiction. It is thought that nicotine-preffered animals tend to consume more nicotine to compensate for this hypodopaminergic state. Research was supported and approved by Ege University, Scientific Research Projects Commission (Grant:29642) and Animal Ethics Committee (EÜHADYEK 2024-051).

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