The different role of G-protein-coupled receptor 30 (GPR30) in the interaction effects of marijuana and estradiol on spatial learning and memory at different ages

Abstract

Some studies suggest that the effect of cannabis on behavior performance depends on the presence of ovarian hormones and the age of use initiation. Estradiol is the main ovarian hormone that can interact with cannabinoids. It has been suggested that cannabinoids exert some of their effects directly through estrogen receptors (ERs). A novel G-protein-coupled receptor (GPR30) was described as mediating estrogen signaling in various cell lines. Since there are few studies on the interaction of cannabis and ovarian hormones on cognitive behaviors, so, this study evaluated the role of GPR30 in the effects of marijuana (M) and estrogen, alone and in combination, on spatial learning and memory of young (non-ovarian(OVX)) and old female rats. Young (5–7 months) and old (22–24 months) female rats received an intraperitoneal injection (i.p) of 17β-estradiol (E2), G1 (GPR30 agonist), and G15 (GPR30 antagonist) every four days, and M (every day), either alone or in combination, for 28 days. One hour after the last injection, the Morris water maze (MWM) test was conducted to evaluate of spatial learning and memory. Moreover, hippocampal BDNF level was assessed by the ELISA method. The results showed a positive effect of M on spatial learning in both young and old rats, however, E2 showed beneficial effects on the memory of young, but not old rats. Our results showed that GPR30 does not have any role in the interaction effects of M and E2 in young rats. Although both E2 and M alone showed positive effects on spatial learning and memory in old rats, however, our results showed a negative interaction between marijuana and E2 combined effects on spatial learning and memory in old female rats which is mediated by GPR30. Our results showed that the effects of GPR30 on spatial learning and memory is age dependent. Furthermore, this study showed that hippocampal BDNF does not have any role in the interaction effects of M and E2 on spatial learning and memory in young and old rats