scholarly journals Requirement of Cannabinoid Receptor Type 1 for the Basal Modulation of Hypothalamic-Pituitary-Adrenal Axis Function

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1574-1581 ◽  
Author(s):  
Daniela Cota ◽  
Michel-Alexander Steiner ◽  
Giovanni Marsicano ◽  
Cristina Cervino ◽  
James P. Herman ◽  
...  

The endocannabinoid system affects the neuroendocrine regulation of hormone secretion, including the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, the mechanisms by which endocannabinoids regulate HPA axis function have remained unclear. Here we demonstrate that mice lacking cannabinoid receptor type 1 (CB1−/−) display a significant dysregulation of the HPA axis. Although circadian HPA axis responsiveness is preserved, CB1−/− mice are characterized by an enhanced circadian drive on the HPA axis, resulting in elevated plasma corticosterone concentrations at the onset of the dark as compared with wild-type (CB1+/+) littermates. Moreover, CB1−/−-derived pituitary cells respond with a significantly higher ACTH secretion to CRH and forskolin challenges as compared with pituitary cells derived from CB1+/+ mice. Both CBL−/− and CB1+/+ mice properly respond to a high-dose dexamethasone test, but response to low-dose dexamethasone is influenced by genotype. In addition, CB1−/− mice show increased CRH mRNA levels in the paraventricular nucleus of the hypothalamus but not in other extrahypothalamic areas, such as the amygdala and piriform cortex, in which CB1 and CRH mRNA have been colocalized. Finally, CB1−/− mice have selective glucocorticoid receptor mRNA down-regulation in the CA1 region of the hippocampus but not in the dentate gyrus or paraventricular nucleus. Conversely, mineralocorticoid receptor mRNA expression levels were found unchanged in these brain areas. In conclusion, our findings indicate that CB1 deficiency enhances the circadian HPA axis activity peak and leads to central impairment of glucocorticoid feedback, thus further outlining the essential role of the endocannabinoid system in the modulation of neuroendocrine functions.

2019 ◽  
Vol 35 (3) ◽  
pp. 516-529 ◽  
Author(s):  
Fernanda Crunfli ◽  
Talita A. Vrechi ◽  
Andressa P. Costa ◽  
Andréa S. Torrão

Diabetes ◽  
2009 ◽  
Vol 59 (2) ◽  
pp. 375-385 ◽  
Author(s):  
C. Lipina ◽  
C. Stretton ◽  
S. Hastings ◽  
J. S. Hundal ◽  
K. Mackie ◽  
...  

2017 ◽  
Vol 112 (6) ◽  
pp. 933-939 ◽  
Author(s):  
Andrzej Wasilewski ◽  
Urszula Lewandowska ◽  
Paula Mosinska ◽  
Cezary Watala ◽  
Martin Storr ◽  
...  

2020 ◽  
Vol 34 (4) ◽  
pp. 429-440
Author(s):  
Lucas Gomes-de-Souza ◽  
Willian Costa-Ferreira ◽  
Leandro A Oliveira ◽  
Ricardo Benini ◽  
Carlos C Crestani

Background: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. Aims: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. Methods: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Results: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Conclusions: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.


Author(s):  
Trenton C. Simmons ◽  
Sara M. Freeman ◽  
Nicholas S. Lackey ◽  
Brooke K. Dreyer ◽  
Devanand S. Manoli ◽  
...  

2018 ◽  
Vol 92 (9) ◽  
pp. 2885-2896 ◽  
Author(s):  
Yaochen Zhang ◽  
Don-Kyu Kim ◽  
Yoon Seok Jung ◽  
Yong-Hoon Kim ◽  
Yong Soo Lee ◽  
...  

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