Details

Autor(en) / Beteiligte

• Chang, Heng-Ai
• Dai, Wen
• Hu, Sherry Shu-Jung

Titel

Sex differences in cocaine-associated memory: The interplay between CB1, mGluR5, and estradiol

Ist Teil von

• Psychoneuroendocrinology, 2021-11, Vol.133, p.105366-105366, Article 105366

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• We know surprisingly little about the sex differences in the neurobiology of cocaine addiction, except females are more susceptible to the rewarding effects of cocaine than their male counterparts. Only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents. We contribute to this emerging line of research by documenting sex differences in cocaine-associated memory and illustrating the underlying signaling pathways in five experiments. Rimonabant (Rim), a cannabinoid CB1 antagonist and inverse agonist, exerted a facilitating effect for low-dose cocaine and an impairing effect for high-dose cocaine CPP memory in male mice, as in our previous study, but not in female mice. Nor did we observe the effect exist among CB1 knockout male mice, which indicated that the CB1 receptors played a mediating role. We also found that the metabotropic glutamate receptor 5 (mGluR5) was located in the same signaling pathway as CB1 in male mice. To clarify the mechanisms behind the sex differences, we used ovariectomized (OVX) female mice with estradiol benzoate (EB) replacement. In the OVX female mice, we showed that Rim-alone and EB-alone, but not Rim-and-EB-combined, facilitated the low-dose cocaine CPP memory. Moreover, 4-hydroxytamoxifen (4-OHT), an estrogen receptor (ER) antagonist, blocked Rim's and EB's facilitating effect. Finally, 2-methyl-6-(phenylethynyl)pyridine (MPEP), an mGluR5 antagonist, partially blocked EB’s facilitating effect. In sum, we identified sex-specific effects of Rim on cocaine-induced CPP memory and the respective signaling pathways: mGluR5-CB1 for male mice and ER-mGluR5-CB1 for female mice. These findings may have merits for the development of sex-specific treatment for cocaine addiction. ●Females are more susceptible to the rewarding effects of cocaine than their male counterparts.●However, we know surprisingly little about the sex differences in the neurobiology of cocaine addiction, and only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents.●We contribute to this emerging line of research by documenting sex differences in cocaine-induced CPP memory and illustrating the underlying signaling pathways.●We identified sex-specific effects of rimonabant (Rim), a cannabinoid CB1 antagonist and inverse agonist, on cocaine-induced CPP memory and the respective signaling pathways involving metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor (ER): mGluR5-CB1 for male mice and ER-mGluR5-CB1 for female mice.●We believe this novel discovery of Rim’s sex-specific signaling pathways in cocaine-associated memory may have implications for the development of sex-specific treatment for cocaine addiction.