Introduction:
The endocannabinoid system has emerged as an important modulator of neuroendocrine regulation of hormone secretion, including the hypothalamic-pituitary-adrenal (HPA) axis. This axis, responsible for maintaining homeostatic balance in response to stressful stimuli, has its activity finely regulated by several limbic brain structures, such as the hippocampus, amygdala and prefrontal cortex. However, the mechanisms by which endocannabinoids regulate the HPA axis are not yet fully elucidated. (COTA et al., 2007)
Unraveling the Role of the CB1 Receptor in HPA Axis Activity:
Recent studies have demonstrated that mice deficient in cannabinoid receptor type 1 (CB1) exhibit significant dysregulation of the HPA axis. Despite maintaining circadian responsiveness of the HPA axis, these mice exhibit increased circadian activity of the axis, resulting in elevated plasma corticosterone concentrations at the onset of the dark phase, compared to wild-type mice (COTA et al., 2007).
Impact of CB1 Deficiency on HPA Axis Response:
CB1 deficiency also affects the HPA axis response to the dexamethasone suppression test. While CB1 knockout and wild-type mice respond adequately to high doses of dexamethasone, the response to low doses is influenced by the absence of the CB1 receptor. Furthermore, CB1 knockout mice have increased levels of CRH mRNA in the paraventricular nucleus of the hypothalamus, but not in other extrahypothalamic areas, such as the amygdala and piriform cortex, where CB1 and CRH mRNA were co-localized. (COTA et al., 2007)
Effects of CB1 Deficiency on Glucocorticoid Receptor Expression:
Another important finding is the selective reduction of glucocorticoid receptor mRNA in the CA1 region of the hippocampus in CB1 knockout mice, without changes in mineralocorticoid receptor mRNA expression in the brain areas evaluated. (COTA et al., 2007)
Conclusion:
In summary, CB1 deficiency increases the circadian peak activity of the HPA axis and leads to central impairment of glucocorticoid feedback, highlighting the essential role of the endocannabinoid system in modulating neuroendocrine functions, with implications for the understanding and treatment of stress-related diseases. (COTA et al., 2007)
Reference:
COTA, D. et al. Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology, vol. 148, n. 4, p. 1574-1581, 2007.
