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Sex, THC, and hormones: Effects on density and sensitivity of CB1 cannabinoid receptors in rats.
- Source :
-
Drug & Alcohol Dependence . Jan2019, Vol. 194, p20-27. 8p. - Publication Year :
- 2019
-
Abstract
- <bold>Background: </bold>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 Δ9-tetrahydrocannabinol (THC) effects, we examined the effects of sex and gonadal hormones on CB1 receptors in cerebellum, hippocampus, prefrontal cortex, and striatum.<bold>Methods: </bold>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 [35S]GTPγS and [3H]SR141716A saturation binding assays were performed.<bold>Results: </bold>With exception of enhanced receptor activation in the hippocampi of female rats compared to males, vehicle-treated rats exhibited minimal sex differences in CB1 receptor densities or G-protein coupling. Repeated treatment with THC resulted in pronounced CB1 receptor desensitization and downregulation in both sexes in all brain regions with a greater magnitude of change in females.<bold>Conclusions: </bold>These results suggest that sex differences in the density and G-protein coupling of brain CB1 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SEX (Biology)
*CANNABINOID receptors
*SEX hormones
*HORMONES
*BINDING site assay
*DRUG metabolism
*ANIMAL experimentation
*ANIMALS
*BIOCHEMISTRY
*BRAIN
*CANNABINOIDS
*CELL receptors
*DRUG tolerance
*DRUGS
*ESTRADIOL
*HUMAN reproduction
*PHENOMENOLOGY
*NEUROTRANSMITTERS
*RATS
*RESEARCH funding
*TESTOSTERONE
*PHARMACODYNAMICS
*PHYSIOLOGY
BRAIN metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 03768716
- Volume :
- 194
- Database :
- Academic Search Index
- Journal :
- Drug & Alcohol Dependence
- Publication Type :
- Academic Journal
- Accession number :
- 133766206
- Full Text :
- https://doi.org/10.1016/j.drugalcdep.2018.09.018