title: Hippocampal type I and type II corticosteroid receptors are differentially regulated by chronic prazosin treatment.
abstract: Two types of hippocampal corticosteroid receptors play an important role in regulating the secretion of corticosterone: type I receptors are thought to regulate both the basal and stress induced release of corticosterone whereas type II receptors seem to be involved only in the stress response. Although these receptors are known to be regulated by circulating levels of corticosterone, there is also evidence for a direct neural control independent of hormonal influences. Furthermore, several studies suggest differential regulation of type I and type II corticosteroid receptors, with greater hormonal control of type II and greater neural control of type I. In order to investigate this theory of differential regulation of type I and type II corticosteroid receptors, we studied the effect of chronic treatment with either vehicle or the alpha 1 noradrenergic antagonist prazosin (0.5 mg/kg, i.p), on hippocampal corticosteroid receptors. Rats in one group had intact adrenal glands, whereas rats in a second group were adrenalectomized, their plasma corticosterone levels being maintained in the physiological range by implantation of corticosterone pellets. Thus, in the first group, the effects of drug-induced changes in both noradrenergic transmission and corticosterone secretion on corticosteroid receptors were investigated, whereas in the second group, the influence of altered noradrenergic transmission was effectively isolated. The results of this experiment show that, in comparison to the vehicle treatment, chronic treatment with the alpha 1 receptor antagonist prazosin decreased the number of type I corticosteroid receptors in adrenalectomized animals with corticosterone substitutive therapy. This effect on type I was not evident in adrenal-intact animals. In contrast, the prazosin treatment reduced the number of type II corticosteroid receptors in adrenal-intact animals, but not in adrenalectomized animals with corticosterone substitutive therapy. It has also been demonstrated here that, in the adrenal-intact animals, chronic prazosin induces hypersecretion of corticosterone after stress, which may account for the reduction of type II corticosteroid receptors noted in this group. Taken together, these results support the theory that type I and type II are differentially regulated: type I receptors can be regulated by noradrenaline independently of corticosterone, whereas type II receptors seem to be adjusted by circulating levels of corticosterone. These results may also suggest possible pharmacotherapies of hypothalamo-pituitary-adrenal axis dysregulation, such as that occurring during depression, Alzheimer's disease and Cushing syndrome, by targeting type I corticosteroid receptors.
authors.affiliation: Laboratoire de Psychobiologie des Comportements Adaptatifs, INSERM U259, Université de Bordeaux II, France.
authors.forename: M
authors.initials: M
authors.lastname: Kabbaj
authors.forename: M
authors.initials: M
authors.lastname: Le Moal
authors.forename: S
authors.initials: S
authors.lastname: Maccari
mesh_terms: D000315:Adrenalectomy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000187:drug effects*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism; D013997:Time Factors
chemical_list: D000317:Adrenergic alpha-Antagonists; D011987:Receptors, Steroid; D003345:Corticosterone; D011224:Prazosin