Figure 1. Sex- and estrous cycle-dependent alterations in hippocampal glutamate receptor expression.

Sex differences in expression of both metabotropic and ionotropic glutamate receptors have been identified within the hippocampus. The metabotropic receptors mGluR2/3 and mGluR5 are expressed at higher levels in females than males (Wang et al., 2015), but how this varies by estrous phase has not been investigated. Conversely, females express lower levels of ionotropic receptors within the hippocampus, but this appears mostly specific to the estrus phase of the estrous cycle (Palomero-Gallagher et al., 2003). Expression levels of ionotropic receptors have not been assessed for the either proestrus or metestrus, thus it remains unclear how the surge in estradiol and progesterone that occur during proestrus may alter expression patterns. These sex- and estrous cycle-dependent differences may underlie differential risk for addictive behavior and/or variance in response to treatment. Lines represent approximate increases or decreases in glutamate receptor expression in the hippocampus in males versus females and across the estrous cycle. Dashed lines represent receptor expression levels for which estrous cycle has not been assessed.