The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic–pituitary–adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46365/1/213_2005_Article_2164.pd

Effect of posterior pituitary denervation (PPD) on prolactin (PRL) and α-melanocyte-stimulating hormone (α-MSH) secretion of lactating rats

Previous data have clearly suggested that the posteriorpituitary (PP), consisting of neural lobe (NL) and intermediatelobe (IL), has a role in the control of anterior pituitaryPRL secretion. However, basic aspects of this regulatory mechanismlike (1), the role of an intact hypothalamic innervation ofthe PP as well as (2) the site of production of previously foundPRL releasing substance(s) have not yet been characterized.Denervation of the PP (PPD) is an effective method for having aselective lesion of the innervation of PP, indeed, PPD results ina disappearance of neurosecretory materials from NL and tyrosinehydroxylase (TH) immunoreactivity from IL, leaving bloodsupply of all three lobes intact. Blood samples were taken fromfreely moving sham and PP-denervated lactating rats before andafter 4-h separation from their pups and during the sucklingstimulus. PPD blocks separation-induced depletion but only attenuatessuckling induced release of PRL. Furthermore, it doublesplasma level of a-MSH during the entire sampling period,which has been used as a marker for in vivo secretory activityof IL cells. Lack of the separation-induced depression in plasmaPRL of PPD animals can be partially restored by normalizing thediabetes insipidus with treatment of a vasopressin analogue, 1-desamino-8-D-arginine-vasopressin (dDAVP). In contrast, d-DAVP, neither alone nor in combination with oxytocin (OXY), canchange PPD-induced elevation of plasma a-MSH as well as attenuationof PRL response induced by suckling. It is concludedthat: (1) contribution of the THDA system parallel to the confirmedrole in the regulation of a-MSH seems to be crucial forthe depletion of plasma PRL induced by separation but not forthe elevation due to suckling stimulus, (2) intact hypothalamicinnervations of both NL and IL, regulating water intake and thesecretion of a-MSH, respectively, are necessary for normal secretoryresponses of AL during lactation, (3) as well as for thepresence of PRF activity in PP, (4) which does not solely responsiblefor suckling-induced PRL release. Therefore, an interplaybetween several substances produced by NIL of the pituitarygland must have been responsible for the intactregulation of PRL secretion during lactation