Dopamine and Norepinephrine Tissue Levels in the Developing Limbic Brain Are Impacted by the Human 6 3'-UTR Single-Nucleotide Polymorphism (rs2304297) in Rats

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Apr 13

PMID 38612487

Authors

Diana Carreno

Antonella Facundo

My Trang Thi Nguyen

Shahrdad Lotfipour

Affiliations

Soon will be listed here.

Abstract

We previously demonstrated that a genetic single-nucleotide polymorphism (SNP, rs2304297) in the 3' untranslated region (UTR) of the human 6 gene has sex- and genotype-dependent effects on nicotine-induced locomotion, anxiety, and nicotine + cue-induced reinstatement in adolescent rats. This study aims to investigate how the 6 3'-UTR SNP influences dopaminergic and noradrenergic tissue levels in brain reward regions during baseline and after the reinstatement of drug-seeking behavior. Naïve adolescent and adult rats, along with those undergoing nicotine + cue reinstatement and carrying the 6 3'-UTR SNP, were assessed for dopamine (DA), norepinephrine (NE), and metabolites in reward pathway regions. The results reveal age-, sex-, and genotype-dependent baseline DA, NE, and DA turnover levels. Post-reinstatement, male α6 rats show suppressed DA levels in the Nucleus Accumbens (NAc) Shell compared to the baseline, while nicotine+ cue-induced reinstatement behavior correlates with neurotransmitter levels in specific brain regions. This study emphasizes the role of 6 3'-UTR SNP in the developmental maturation of the dopaminergic and noradrenergic system in the adolescent rat brain, with tissue levels acting as predictors of nicotine + cue-induced reinstatement.

Citing Articles

Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized 6 3'-UTR SNP (rs2304297) adolescent rats.

Carreno D, Facundo A, Cardenas A, Lotfipour S Front Pharmacol. 2024; 15:1445303.

PMID: 39206256 PMC: 11349519. DOI: 10.3389/fphar.2024.1445303.

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