Long-term tamoxifen effects in the cyclic interaction of the endocannabinoid and endocrine system in the rat central nervous system

Abstract

Steroid hormones can modulate the endocannabinoid system (ECS). Within the female repro-ductive tract, estrogen increases the expression of the cannabinoid receptors CB1 and CB2, and modifies the levels of anandamide (AEA), the major endocannabinoid, by altering the expres-sion of both AEA synthesis (NAPE-PLD) and catabolic enzymes (FAAH). Here, we addressed the mechanisms involved in ECS fluctuations within central nervous system and evaluated the ef-fects of tamoxifen (TAM), a selective estrogen receptor modulator, in the central AEA regulation. The current results suggest that the hypothalamic and pituitary AEA levels change differently according to the brain area and phase of the estrous cycle. In TAM-treated rats, there is a disrup-tion of the cyclic fluctuation and reduction of the AEA levels in all brain areas. In pituitary, NAPE-PLD expression increases in metestrus phase, whereas throughout rat cycle, their expres-sion remained constant, even upon TAM treatment. The fluctuations of pituitary AEA levels re-sult from altered FAAH and NAPE-LPD expression. In contrast, no differences in FAAH or NAPE-PLD hypothalamic expression were observed. Overall, this study presents a broad view of the distribution and expression of ECS elements in the central nervous system and a way to suggest possible brain areas involved in the interaction of the endocannabinoid and neuroendo-crine systems to induce several behavioral responses.