Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction. The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glutamate receptor type 5 (mGluR5). However, the downstream effectors of this ER/mGluR5 signaling pathway are unknown. Here we investigate whether cannabinoid 1 receptor (CB1R) activation is a part of the mechanism whereby estradiol influences behavioral and synaptic correlates of addiction. Following repeated cocaine administration, estradiol-treated ovariectomized rats exhibited both sensitized locomotor responses and decreases in the dendritic spine density of nucleus accumbens core medium-spiny neurons in comparison to oil-treated controls. Both effects of estradiol were blocked by AM251, a CB1R inverse agonist. These results indicate that part of the signaling mechanism through which estradiol impacts behavioral and synaptic correlates of addiction in female rats requires activation of CB1Rs.
Bibliographical noteFunding Information:
This material is based upon work supported by the National Institutes of Health DA035008 (PGM and RLM) and DA040345-01 (BMP) a National Science Foundation Grant No. 00006595 (BMP). We would like to thank Ambrosia Smith, Sonal Napgal and Holly Korthas for assistance with data collection.
© 2016 Elsevier Ltd
- Behavioral sensitization
- Dendritic spine plasticity
- Drug addiction
- Nucleus accumbens core
- Type 1 cannabinoid receptors