Distinct gene alterations between Fos‐expressing striatal and thalamic neurons after withdrawal from methamphetamine self‐administration

Abstract

Background Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving). We previously demonstrated a role of anterior intralaminar nucleus of thalamus (AIT) to dorsomedial striatum (DMS) projections in this incubation. Here, we examined molecular alterations in DMS and AIT neurons activated (identified by neuronal activity marker Fos) during “incubated” Meth‐seeking relapse test after prolonged withdrawal. Methods We trained male rats to self‐administer Meth or saline (control condition) for 10 days (6 hr/day). Using fluorescence‐activated cell sorting, we examined gene expression in Fos‐positive (activated during a 2‐hr relapse test) and Fos‐negative (nonactivated) DMS and AIT neurons. Results In DMS, we found increased mRNA expressions of immediate early genes (IEGs) (Arc, Egr1, Npas4, Fosb), Trkb, glutamate receptors subunits (Gria3, Grin1, Grin2b, Grm1), and epigenetic enzymes (Hdac3, Hdac5, Crebbp) in Fos‐positive neurons, compared with Fos‐negative neurons. In AIT, we found that fewer genes (Egr1, Fosb, TrkB, Grin1, and Hdac5) exhibited increased mRNA expression in Fos‐positive neurons. Unexpectedly, in both brain regions, gene alterations described above also occurred in drug‐naïve saline self‐administration control rats. Conclusions These results demonstrated that transcriptional regulations in Fos‐positive neurons activated during the relapse tests are brain region‐specific but are not uniquely associated with drug exposure during the self‐administration training.

Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine Seeking in a Rat Model

“…Given our previous work and work from others indicating a role for Grin1 /NR1 in cocaine seeking and the efficacy of exercise in reducing cocaine seeking ( 18 , 70 , 74 ), Grin1 transcription was visualized using IGV. This analysis revealed that the normalized mapped read densities for the sedentary and exercise conditions varied significantly by exon ( Figure 4F ).…”

Regional Homogeneity Abnormalities and Its Correlation With Impulsivity in Male Abstinent Methamphetamine Dependent Individuals

“…A challenge for treating MA abuse is recurrence during abstinence ( Li X. et al, 2019 ). Although many factors contribute to recurrence of MADs, a possible key predictor is impulsivity ( Ahn et al, 2016 ; Vassileva and Conrod, 2019 ).…”

The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3

“…In the METH-induced conditioned place preference (CPP) model, an increased histone 3 acetylation was identified in the limbic forebrain of mice and found in specific gene-promoter regions related to synaptic plasticity, such as Nrxn, Gria1, Grin2a, and Grin2b, thus indicating its essential role in METH dependence ( 15 ). An increased expression of HDAC3 mRNA has been noted in Fos-positive neurons in the dorsomedial striatum after withdrawal following METH self-administration ( 16 ). Studies have shown that sodium butyrate, a non-selective inhibitor of class I/II HDACs, can help overcome a previously established CPP and suppress the reinstatement of METH-induced CPP ( 17 ).…”