Open AccessDistinct gene alterations between Fos‐expressing striatal and thalamic neurons after withdrawal from methamphetamine self‐administration
Author(s) -
Li Xuan,
Davis Ian R.,
Lofaro Olivia M.,
Zhang Jianjun,
Cimbro Raffaello,
Rubio F. Javier
Publication year - 2019
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.1378
Subject(s) - fosb , methamphetamine , meth , immediate early gene , striatum , glutamate receptor , biology , endocrinology , c fos , medicine , gene expression , pharmacology , chemistry , receptor , dopamine , gene , genetics , monomer , organic chemistry , acrylate , polymer
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.