Abstract:
:We have examined the effects of acute administration of the cannabinoid receptor type 1 (CB(1)) antagonist AM251 on the rat hypothalamic-pituitary-adrenal (HPA) axis with respect to both gender and time of day. Blood samples were collected from conscious male and female rats every 5 min using an automated blood sampling system, and corticosterone concentrations were determined. In male rats, there was a distinct diurnal effect of AM251 with a greater activation of the HPA axis in the morning (diurnal trough) compared with the evening (diurnal peak). At both times of the day, circulating corticosterone concentrations were elevated for approximately 4 h after AM251 administration. In female rats, there was also diurnal variation in the activation of the HPA axis; however, these effects were not as profound as those in males. Corticosterone concentrations were only slightly elevated at the diurnal trough and for a shorter time period than in males (2 compared with 4 h). Moreover, there was no effect of AM251 on corticosterone concentrations when administered at the diurnal peak. Subsequent studies, only in males, in which both ACTH and corticosterone were measured, confirmed that the effects of AM251 on corticosterone were mediated by ACTH. Moreover, the elevation of both ACTH and corticosterone could be replicated using another CB(1) antagonist, AM281. These data demonstrate that the extent and duration of HPA axis activation after CB(1) blockade are clearly dependent on both gender and time of day.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Atkinson HC,Leggett JD,Wood SA,Castrique ES,Kershaw YM,Lightman SLdoi
10.1210/en.2010-0101subject
Has Abstractpub_date
2010-08-01 00:00:00pages
3720-7issue
8eissn
0013-7227issn
1945-7170pii
en.2010-0101journal_volume
151pub_type
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