THE EFFECTS OF CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 AND NONMUSCLE MYOSIN II IN DRUG-ASSOCIATED MEMORIES

Substance use disorders (SUDs) are perpetuated by the formation of drug-associated memories. Methamphetamine (METH)-associated memories undergo immediate and long-lasting disruption after treatment with blebbistatin (blebb), a nonmuscle myosin II (NMII) inhibitor, but cocaine (COC) associated memories do not. This suggests that the mechanisms of METH and COC-associated memories are different. To visualize these potential differences, RNA-sequencing was conducted. Crhr2, a gene that encodes corticotropin releasing factor receptor 2 (CRF2), was uniquely upregulated in the BLA after METH learning. Action upon CRF2 after memory consolidation did not have an effect. However, pretreating brains with CRF2 antagonist Astressin-2B (AS2B) prevented blebb’s ability to disrupt established METH-associated memories. Additionally, overexpressing CRF2 in the basolateral amygdala (BLA) plus providing its ligand UCN3 during conditioning, and then administering blebb resulted in disruption of COC-associated memory. CRF2 is the first upstream regulator of NMII inhibition of METH-associated memory to be identified.