Context
The endocannabinoid system (ECS) consists of cannabinoid receptors, endocannabinoids (such as anandamide and 2-arachidonoylglycerol), and metabolic enzymes. The ECS modulates various physiological processes, including synaptic plasticity, learning, motivation, reward, emotional and non-emotional memory, and neurogenesis. Dysfunction in endocannabinoid signaling is linked to neurological and mood disorders, as observed in paranoid-type schizophrenic patients and those with unipolar depression. Medical use of cannabinoids is controversial, but cannabinoids have been approved for treating spasticity, neuropathic pain in multiple sclerosis, and severe childhood epilepsy with non-psychotropic cannabinoid cannabidiol (CBD).
The ECS interacts with gonadal hormones, with estrogen affecting the expression of cannabinoid receptors and metabolic enzymes in female reproductive tissues. Estrogen’s influence on the ECS extends to the hypothalamus, where anandamide levels increase before puberty, suggesting a role in the onset of puberty. Ovarian steroid hormones and endocannabinoids interact, affecting plasma levels of hormones like luteinizing hormone, follicle-stimulating hormone, and estradiol.
Tamoxifen (TAM), an estrogen receptor modulator used in breast cancer therapy, improves disease-free survival but is associated with mood disorders and cognitive impairments. The preoptic area and hypothalamus, crucial in regulating motivated behaviors and emotional responses, express estrogen receptors abundantly.
The study aims to investigate the effects of long-term TAM therapy on ECS components’ expression in the preoptic area and hypothalamus, exploring the connection between TAM, estrogen receptors, and the modulation of pathways involved in mood disorders and cognition using an animal model
