Cannabinoid receptor 1 (CB1) signaling acts as a major regulatory mechanism of hypothalamus–pituitary–adrenal (HPA) axis mediated corticosterone secretion

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  • (mPFC). To measure changes in neuronal activation inthese areas, cFos expression was assessed before and aftersingle or repeated rehydration in water restricted (WR) rats.Adult male rats were water deprived for 1 day and sacricedbefore or 1 h after 15 min of drinking. Another group ofrats was water restricted for 6 days by limiting access towater to 30 min/day. On day 6, rats were sacriced beforeor 1 h after 15 min of drinking. Control rats had access towater ad libitum. WR for 1 or 6 days increased cFos inthe MnPO and prelimbic (pl)PFC. Expression of cFoswas greater at 1 vs 6 days, suggesting habituation to WRin these areas. No change in cFos expression was observedin the infralimbic (il)PFC in response to WR. A single epi-sode of rehydration increased cFos in the plPFC and ilPFCand decreased cFos in the MnPO. After repeated rehydra-tion, cFos increased in the plPFC, but did not change inthe MnPO or ilPFC. These data show that repeated rehy-dration alters cFos expression in brain areas that mediatedehydration-induced changes in HPA activity and in limbicareas associated with conditioned appetitive responses.These ndings implicate these structures as potential candi-dates for projection neurons that could contribute to thedierential response of mpPVN neurons to repeated rehy-dration. (Supported in part by NSF IBN 0112543 andNIDA T32DA07097(MMA).)


    Cannabinoid receptor 1 (CB1) signaling acts as a major

    regulatory mechanism of hypothalamuspituitaryadrenal

    (HPA) axis mediated corticosterone secretion

    M. Steiner a, G. Marsicano b, F. Holsboer a, B. Lutz b,

    C.T. Wotjak a

    a Max-Planck-Institute of Psychiatry, Munich, Germanyb Johannes-Gutenberg University, Mainz, Germany

    The endocannabinoid system has been implicated in thebehavioral response to dierent kinds of stressors as wellas in the regulation of stress-induced hormonal reactions.However, little is known about the time course of theseeects, the inuence of gender and dierences between genet-ic inactivation and pharmacological blockade of CB1receptors.

    We demonstrate that the circadian cycle of corticoste-rone was maintained in male and female CB1 knockout(CB1/) mice and wild-type littermates (CB1+/+). Howev-er, CB1/mice showed a dysregulation of the HPA axis atthe circadian peak when they displayed elevated corticoste-rone levels compared to CB1+/+. No dierence betweengenotypes could be observed at the circadian trough.Repeated administration of the CB1 receptor antagonistSR141716A likewise resulted in elevations of corticoste-rone compared to vehicle treated controls in both gendersduring the second half of the nocturnal phase.

    Forced swim stress resulted in a signicantly strongerincrease of corticosterone 30 min after the stressor in

    CB1/ as well as in SR141716A treated animals of bothsexes compared to their respective controls. In general,corticosterone levels returned to pre-stress values within2 h. However, corticosterone levels were still signicantlyhigher in male SR141716A treated mice compared to theircontrols.

    Also ACTH plasma levels were signicantly increased30 min after forced swimming but signicant dierencescould be observed only in female CB1/ mice, whichshowed higher ACTH levels than CB1+/+ littermates.

    To assess early HPA axis responses and possibleSR141716A eects on potential cannabinoid receptors dif-ferent from CB1, female CB1+/+ and CB1/ mice weretreated with SR141716A and killed directly after the stress-or. Both genetic ablation and pharmacological blockade ofCB1 resulted in elevated corticosterone levels, whereasSR141716A was without any eect in CB1/ animals.No dierences between groups could be observed in ACTHlevels.

    The similarities of CB1 receptor inactivation by geneticand pharmacological means led us to conclude that CB1receptor signaling represents an important regulatory con-straint of corticosterone secretion under basal as well asunder stressful conditions, independent of gender. The bio-logical mechanisms responsible for these eects remain tobe identied, but the largely unaected ACTH responsesmay argue for the involvement of the endocannabinoidsystem in the adrenal glands.


    Modulating the stress hormone response to exercise in pigs

    Ryan Jankord, V.K. Ganjam, R.M.McAllister,M.H. Laughlin

    Department of Biomedical Sciences, University of Missouri,


    During exercise tests to determine maximal oxygen con-sumption it was observed that pigs had a greater ACTHand cortisol response than previously recorded for otherexercising mammals. At pre-exercise, 4.8, 8.0, and11.3 km/h, and maximal exercise the ACTH response was62 6, 149 22, 317 82, 656 133, and 968 306pg/ml, while the cortisol response was 122 15,210 32, 240 44, 249 43, and 203 36 ng/ml, respec-tively. We hypothesized that the physical demand of exer-cise was not the major contributor to the exaggeratedACTH and cortisol response; rather, we proposed that psy-chological stressors associated with the exercise test,including the presence of multiple personnel, the use ofelectrical stimulation (agricultural prodder on rear) andverbal encouragement for continued running and the factthat animals had run to exhaustion the previous day, weresignicant contributors to the measured concentrations ofACTH and cortisol. We proposed that removing theseadditional stressors would greatly reduce the ACTH andcortisol response to forced exercise in pigs so that the

    Abstracts / Frontiers in Neuroendocrinology 27 (2006) 3862 39


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