Accepted manuscript
Sex, THC, and hormones: Effects on density and sensitivity of CB 1 cannabinoid receptors in rats
Drug and alcohol dependence, Vol.194, pp.20-27
01/01/2019
Handle:
https://hdl.handle.net/2376/116504
PMID: 30391834
Abstract
The recent NIH mandate to consider sex as a biological variable in preclinical research has focused attention on delineation of sex differences in behavior. To investigate mechanisms underlying sex differences in Δ
-tetrahydrocannabinol (THC) effects, we examined the effects of sex and gonadal hormones on CB
receptors in cerebellum, hippocampus, prefrontal cortex, and striatum.
Adult Sprague-Dawley rats underwent gonadectomy (GDX) or sham-GDX. Half of the GDX females and males received estradiol or testosterone replacement (GDX+H), respectively. All rats were injected with vehicle or 30 mg/kg THC twice daily for 1 week before brain collection. CP55,940-stimulated [
S]GTPγS and [
H]SR141716A saturation binding assays were performed.
With exception of enhanced receptor activation in the hippocampi of female rats compared to males, vehicle-treated rats exhibited minimal sex differences in CB
receptor densities or G-protein coupling. Repeated treatment with THC resulted in pronounced CB
receptor desensitization and downregulation in both sexes in all brain regions with a greater magnitude of change in females.
These results suggest that sex differences in the density and G-protein coupling of brain CB
receptors may play a limited role in sex differences in acute THC effects not mediated by the hippocampus. In contrast, sex differences after repeated THC were common, with females (intact, GDX, and GDX+H) showing greater downregulation or desensitization in all four brain regions compared to the respective male groups. This result is consistent with a finding that women tend to progress to tolerance and dependence quicker than men after initiation of cannabis use.
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Details
- Title
- Sex, THC, and hormones: Effects on density and sensitivity of CB 1 cannabinoid receptors in rats
- Creators
- Charlotte E Farquhar - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USAChristopher S Breivogel - Department of Pharmaceutical Sciences, Campbell University, Buies Creek, NC 27506, USAThomas F Gamage - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USAElaine A Gay - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USABrian F Thomas - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USARebecca M Craft - Department of Psychology, Washington State University, Pullman, WA 99164-4820, USAJenny L Wiley - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA. Electronic address: jwiley@rti.org
- Publication Details
- Drug and alcohol dependence, Vol.194, pp.20-27
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier; Ireland
- Number of pages
- 8
- Grant note
- R01 DA040460 / NIDA NIH HHS R01 DA016644 / NIDA NIH HHS R01 DA003672 / NIDA NIH HHS R37 DA003672 / NIDA NIH HHS
- Identifiers
- 99900547676101842
- Language
- English
- Resource Type
- Accepted manuscript