Many reasons can contribute to gender differences, such as hormone levels (e.g. estrogen, progesterone), innate differences in neuronal system adaptations, and pharmacokinetics of abused drugs in body (Becker, 1999; Carroll et al., 2004; Russo et al., 2003). Significant gender differences were reported in self-administration of drugs during pharmacological treatment using GABA receptor agonist in rats and kappa opioid receptor agonist in monkeys, which suggest sex-related differences in neurotransmission system. Rodent studies have shown that gender impacts on adaptations in GABA receptors. Female ethanol withdrawn rats showed greater sensitization to endogenous neuroactive steroids, which have selective effects at GABA and N-methyl-d-aspartate receptors (Devaud et al., 1998). In addition, GABAAα4 subunit expression in hippocampus and cerebral cortex were significantly increased in males, but not in females after chronic ethanol administration (Devaud and Alele, 2004). Effects of ethanol withdrawal on gene expression were also different by gender, thus female rats tend to have higher GAD1 level than males in the hippocampus and cerebral cortex, while male rats exhibited higher level of GAD2 than females in both brain areas (Alele and Devaud, 2005). Overall,
