Compulsive methamphetamine taking is associated with differential expression of HDAC2-regulated genes in the rat dorsal striatum

Methamphetamine (METH) use disorder (MUD) is a neuropsychiatric disorder with loss of self-control over drug intake despite of negative consequences. The behavioral consequences of long-term METH intake on compulsive and non-compulsive individuals remain unclear. Herein we trained rats to self-administered METH 1st for 22 days than 8 days of foot-shock and 15 days of abstinence. Which was followed by 12 days of reinstatement to METH self-administration then 3 days of foot-shock and 15 days of abstinence. After 1st foot-shock phase we found two phenotypes based on their METH intake i.e., shock resistance (SR, compulsive), and shock sensitive (SS, non-compulsive). Interestingly during reinstatement of METH self-administration then foot-shock, some (resurgent shock resistance, RSR) non-compulsive rats, displayed compulsive METH intake behavior. During both abstinence period rats were tested for drug seeking behavior and SR rats displayed higher METH seeking then RSR and SS. 24 hour after 2nd withdrawal day testing, we compared transcriptional and epigenetic changes in dorsal striatum. Overall design: Herein we trained rats to self-administered METH 1st for 22 days than 8 days of foot-shock and 15 days of abstinence. Which was followed by 12 days of reinstatement to METH self-administration then 3 days of foot-shock and 15 days of abstinence.