Analysis of the functional role and mRNA expression of GABA B R in the nucleus accumbens of cocaine-addicted rats.

ABSTRACT

BACKGROUND: Drug addiction is a social and medical problem that must be urgently addressed. The nucleus accumbens (NAc) is closely related to addiction-related learning memory, and γ-aminobutyric acid type B receptor (GABA B R) is a potential target for the treatment of drug addiction. However, the role of GABA B R activity levels in the NAc in cocaine addiction is unclear. METHODS: In this study, we established an animal model of cocaine dependence, modulated the level of GABA B R activity, applied a conditioned place preference assay (CPP) to assess the role of the NAc in reconsolidation of addiction memory, evaluated learning and memory functions by behavioral experiments, examined the expression of GB1, GB2, cyclic adenosine monophosphate response element binding protein (CREB), p-CREB, protein kinase A (PKA), protein kinase (ERK), and Brain-derived neurotrophic factor (BDNF) in the NAc by molecular biology experiments, and screened differentially significantly expressed genes by transcriptome sequencing. RESULTS: Our study showed that the GABA B receptor agonist baclofen (BLF) had a significant effect on locomotor distance in rats, promoted an increase in GABA levels and significantly inhibited the PKA and ERK1/2/CREB/BDNF signaling pathways. Moreover, transcriptome sequencing showed that GABA B R antagonist intervention identified a total of 21 upregulated mRNAs and 21 downregulated mRNAs. The differentially expressed (DE) mRNA genes were mainly enriched in tyrosine metabolism; however, further study is needed. CONCLUSION: GABA B R activity in the NAc is involved in the regulation of cocaine addiction and may play an important role through key mRNA pathways.