This Week in The Journal
Journal of Neuroscience
Numerous studies have established that sex hormones, particularly 17b -estradiol, influence many CNS functions, including memory, pain processing, and drug use. Although dissociating biological and societal effects on sex differences in humans is difficult, the physiological bases of estradiol's behavioral effects in rodents have been demonstrated repeatedly. Such studies have revealed, for example, that the motivation to seek cocaine or opiates is greater in female rodents than in males, and
... han in males, and when given free access to ethanol, female mice consume more than males. These behavioral effects likely stem from modulation of dopamine release by estradiol. Previous work by Vandegrift et al. showed that neurons in the ventral tegmental area (VTA), which contains reward-sensitive dopaminergic neurons, were more strongly activated by ethanol in female mice in diestrus, when estrogen levels are high, than in mice in estrus. Furthermore, treating brain slices from ovariectomized female mice with estradiol increased ethanol-induced excitation of VTA neurons. Vandegrift et al. now describe the roles of estrogen receptor a (ERa) and ERbboth of which are expressed in dopaminergic and nondopaminergic neurons in the VTA-in estradiol-dependent modulation of VTA neuron activity and ethanol consumption. Treating brain slices from ovariectomized mice with an ERa agonist significantly increased ethanol-induced excitation of VTA neurons, whereas an ERb agonist had no effect. Furthermore, knocking down ERa or treating slices with an ERa antagonist reduced ethanol-induced excitation of VTA neurons from gonadally intact diestrus mice. In contrast, antagonizing or knocking down ERb had no effect. Finally, knocking down ERa-or, to a lesser extent, ERb -in VTA reduced binge-like alcohol consumption by female mice, whereas knocking down ERa or ERb did not affect ethanol consumption in males. These results suggest that estradiol promotes binge drinking in female mice, but not male mice, by acting on both ERa and ERb in the VTA. The effect of ERa activation is greater, possibly because ERa is more widely expressed in VTA. Activation of ERa makes VTA neurons more sensitive to ethanol, which may make ethanol more rewarding. How ERb increases alcohol consumption remains to be determined.