Estrogenic regulation of limbic cannabinoid receptor binding

Abstract

Sex differences have been identified in many of the behavioral and physiological effects of cannabinoids. While estrogen has been linked to some of these variations, the effects of estrogen on cannabinoid receptor binding have not been characterized within regions of the brain specifically implicated in stress responsivity and emotional behavior. To examine sex differences, and the role of estradiol, in regulation of the cannabinoid receptor, we compared the binding site density of the cannabinoid receptor within the amygdala, hippocampus and hypothalamus in males, cycling females, ovariectomized (OVX) females and estradiol-treated OVX females (OVX+E). Our data reveal that males and OVX females have higher amounts of hypothalamic and lower amounts of amygdalar cannabinoid receptor binding relative to both cycling females and OVX+E females. Within the hippocampus, ovariectomy resulted in an upregulation of cannabinoid receptor binding. These data provide a putative biochemical mechanism mediating the observed behavioral and physiological sex differences in the effects of cannabinoids, particularly with respect to stress and emotional behavior.

Figure 1

Male-female differences in the binding site density of the cannabinoid receptor in limbic forebrain structures: Role of estradiol The maximal binding site density (B_max) of the cannabinoid receptor was examined in the hypothalamus, amygdala and hippocampus of males, cycling females (female), ovariectomized females (OVX female) and ovariectomized/estradiol replaced females (OVX + E female). For all treatment conditions, n = 4-5. Data are presented as means +/− SEM. * denotes significant differences (p < .05) relative to unidentified conditions.