The role of astrocytic adenosine monophosphate-activated protein kinase in cocaine-related behaviors

Abstract

Cocaine use induces changes in the brain’s structure and function inducing long-lasting changes in behavior and cognition. There are no FDA approved treatments for cocaine use disorder. Investigating cocaine-induced neuroadaptations, specifically changes in brain protein expression and function, will inform molecular targets for future therapeutic drug development. Two proteins, glial glutamate transporter 1 (GLT-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) are downregulated upon cocaine exposure. It is unknown whether AMPK, expressed in neurons and astrocytes, regulates GLT-1 in the striatum in a cell-specific manner. I will first determine how astrocyte-specific manipulation of striatal AMPK impacts GLT-1 expression and function in the striatum. I will then determine whether the same astrocytic AMPK manipulations influence cocaine locomotor sensitization and acquisition of cocaine self-administration.