Cannabinoid-mediated regulation of the hypothalamo-pituitary-adrenal axis in rats: age dependent role of vasopressin.
OBJECTIVE
Adaptation to stress is a fundamental component of life and the hypothalamo-pituitary-adrenocortical axis (HPA) plays a crucial role in it. The place of cannabinoid influence seems to be in the brain, especially where corticotropin releasing hormone and vasopressin (AVP) secreting neurons are located. The role of AVP is considered to be more important in young than in adult rats. Here we addressed the question if cannabinoid-mediated regulation of the HPA involves AVP and if there is any difference between young and adult rats in this process.


METHODS
10-day-old and adult AVP deficient Brattleboro rats were compared with their heterozygous littermates 1h after WIN 55,212-2 (6mg/kg i.p.) injection.


RESULTS
In control animals the injection led to elevated adrenocorticotropin (ACTH) and corticosterone hormone levels at both ages without remarkable age difference in ACTH levels while all corticosterone levels of adults was approximately 10-times higher. The ACTH secretion of young AVP deficient rats failed to react to WIN 55,212-2 injection while their corticosterone levels were even higher than their littermates. In contrast in adult the role of AVP was diminished.


CONCLUSIONS
We can conclude that the peripheral administration of cannabinoids leads to HPA axis stimulation, which process involves AVP at least in the young rats. The discrepancy between ACTH and corticosterone levels in young rats suggests an alternative adrenal gland regulatory pathway, which might be present in all studied animals. However, it comes to the front just in AVP deficient pups.
Barna
Istvan
I
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Szigony, Hungary.
Csabai
Katalin
K
Makara
Gabor B
GB
Zelena
Dóra
D
D000311:Adrenal Glands / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000375:Aging / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000172:deficiency / Q000502:physiology*; D048588:Benzoxazines / Q000008:administration & dosage; D002186:Cannabinoids / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D009281:Naphthalenes / Q000008:administration & dosage; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D011910:Rats, Brattleboro; D017208:Rats, Wistar
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D001127:Arginine Vasopressin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone