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

• Published in: Brain and behavior Vol. 9; no. 9; pp. e01378 - n/a
• Main Authors: Li, Xuan, Davis, Ian R., Lofaro, Olivia M., Zhang, Jianjun, Cimbro, Raffaello, Rubio, F. Javier
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2019; John Wiley and Sons Inc; Wiley
• Subjects: Animals; anterior intralaminar nucleus of thalamus; Cocaine; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Craving - physiology; Disease Models, Animal; dorsal striatum; Drug withdrawal; fluorescence‐activated cell sorting; Fos; Gene expression; Gene Expression Regulation - drug effects; Genomes; Hypotheses; incubation of drug craving; Laboratory animals; Male; Methamphetamine; Methamphetamine - administration & dosage; methamphetamine relapse; Neurons - drug effects; Neurons - metabolism; Original Research; Polyethylene; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Roles; Self Administration; Studies; Substance Withdrawal Syndrome - genetics; Substance Withdrawal Syndrome - metabolism; Surgery; Thalamus - drug effects; Thalamus - metabolism; anterior intralaminar nucleus of thalamus; fluorescence-activated cell sorting; dorsal striatum; Fos; methamphetamine relapse; incubation of drug craving
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.1378

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. We used fluorescence‐activated cell sorting and examined gene alterations in dorsomedial striatum (DMS) and anterior intralaminar nucleus of thalamus (AIT) Fos‐positive neurons activated during relapse tests after 1‐month withdrawal from methamphetamine or saline (control condition) self‐administration. We found that DMS and AIT exhibited distinct gene expression profiles in Fos‐positive neurons, compared with Fos‐negative neurons. However, in both brain regions, gene alterations also occurred in the drug‐naïve saline self‐administration control rats.