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.

The anterolateral projections of the medial basal hypothalamus affect sleep.

The role of the medial basal hypothalamus (MBH) and the anterior hypothalamus/preoptic area (AH/POA) in sleep regulation was investigated using the Halász knife technique to sever MBH anterior and lateral projections in rats. If both lateral and anterior connections of the MBH were cut, rats spent less time in non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). In contrast, if the lateral connections remained intact, the duration of NREMS and REMS was normal. The diurnal rhythm of NREMS and REMS was altered in all groups except the sham control group. Changes in NREMS or REMS duration were not detected in a group with pituitary stalk lesions. Water consumption was enhanced in three groups of rats, possibly due to the lesion of vasopressin fibers entering the pituitary. EEG delta power during NREMS and brain temperatures (Tbr) were not affected by the cuts during baseline or after sleep deprivation. In response to 4 h of sleep deprivation, only one group, that with the most anterior-to-posterior cuts, failed to increase its NREMS or REMS time during the recovery sleep. After deprivation, Tbr returned to baseline in most of the treatment groups. Collectively, results indicate that the lateral projections of the MBH are important determinants of duration of NREMS and REMS, while more anterior projections are concerned with the diurnal distribution of sleep. Further, the MBH projections involved in sleep regulation are distinct from those involved in EEG delta activity, water intake, and brain temperature.

Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary-adrenal axis activity in Brattleboro rats.

A growing body of evidence suggests that vasopressinergic activity in the hypothalamus is important in stress-related behaviors (like drug abuse) in line with a role in the regulation of the hypothalamo-pituitary-adrenal axis (HPA). We hypothesized that in the naturally vasopressin-deficient Brattleboro rat, acute and chronic morphine treatment may lead to reduced HPA axis activity. Rats were treated either with a single dose of morphine (10 mg/kg subcutaneously) and serial blood samples were taken or were treated twice daily with increasing doses of morphine (10-100 mg/kg subcutaneously) for 16 days and animals were killed by decapitation 4 or 16 h after the last injection. Single morphine injection induced a biphasic ACTH and corticosterone elevation with smaller increases in vasopressin-deficient rats. Chronic morphine treatment induced the typical somatic and HPA axis changes of chronic stress; the absence of vasopressin did not prevent these changes. In rats repeatedly treated with morphine plasma, ACTH and corticosterone levels were elevated both 4 and 16 h after the last injection (short and long withdrawal) and the absence of vasopressin attenuated this response. Our data suggest that vasopressin plays a prominent role in morphine treatment and withdrawal-induced acute hormonal changes, but does not affect development of chronic hyperactivity of the HPA axis.

Pituitary atrial natriuretic peptide of paraventricular nucleus origin.

Atrial natriuretic peptide-synthesizing neurons in the hypothalamic paraventricular nucleus constitute the major sources of ANP in the three lobes of the pituitary gland. Complete transection of the pituitary stalk eliminated 93% of ANP from the intermediate lobe, 47 and 77% from the anterior and the posterior lobes, respectively. Meantime, increased levels of immunoreactive ANP were measured in the median eminence, due to the accumulation of the peptide in the transected axons centrally to the transected stalk and in the paraventricular nucleus. It is likely that ANP neurons in the paraventricular nucleus innervate the pituitary, but those in the periventricular (median) preoptic nucleus and the organum vasculosum laminae terminalis may not contribute to the ANP innervation of the pituitary gland.