Sex Differences in Psychostimulant Abuse: Implications for Estrogen Receptors and Histone Deacetylases

Substance abuse is a chronic pathological disorder that negatively affects many health and neurological processes. A growing body of literature has revealed gender differences in substance use. Compared to men, women display distinct drug-use phenotypes accompanied by recovery and rehabilitation disparities. These observations have led to the notion that sex-dependent susceptibilities exist along the progression to addiction. Within this scope, neuroadaptations following psychostimulant exposure are thought to be distinct for each sex. This review summarizes clinical findings and animal research reporting sex differences in the subjective and behavioral responses to cocaine, methamphetamine, and nicotine. This discussion is followed by an examination of epigenetic and molecular alterations implicated in the addiction process. Special consideration is given to histone deacetylases and estrogen receptor-mediated gene expression.