We have previously reported that stress induces a rapid increase in hypothalamic somatostatin (SS) release. In the present work, we investigated whether SS synthesis is also affected by this treatment. Male rats were subjected to 15-min immobilization (IMO) stress, and measurements of both SS mRNA levels and SS mRNA-containing cells were analyzed in the periventricular nucleus (PeV) by radioactive and nonradioactive in situ hybridization (ISH), respectively. In addition, SS content and total SS mRNA were measured in the whole hypothalamus by radioimmunoassay (RIA) and northern blot analysis, respectively. ISH was conducted by applying either a radioactive-labeled (35S) or a digoxigenin (DIG)-labeled oligonucleotide probe on histological sections containing the periventricular region of the anterior hypothalamic area (AHA). ISH analysis using radioactive label showed a significant increase in SS mRNA levels in stressed rats. In contrast, stress treatment decreased the number of DIG-labeled cells expressing SS mRNA in this region by 35% as compared to the same histological sections from naive control rats. In addition, a significant decrease in the total SS mRNA DIG-labeled area was observed. Finally, SS content and SS mRNA measured in the whole hypothalamus of stressed rats were markedly inhibited as compared to control rats. Our data show that IMO stress induces a significant and rapid increase in SS mRNA level accompanied by a decrease in the number of cells expressing SS mRNA in the PeV-AHA. The present results suggest that a subset of PeV SS neurons, which became silent at the onset of stress, are regulated independently of the remaining whole mass of PeV neurons. This differential control is in line with the cellular heterogeneity described in periventricular SS-producing neurons and with the multiple hypothalamic and pituitary functions assigned to SS.
Although antidepressant administration has been reported to alter the pituitary adrenal (PA) axis, the results are puzzling. In the present work, two possible factors contributing to these contradictory results were studied in adult male Sprague-Dawley rats: (i) the type of antidepressant and (ii) the time of day at which samples were taken. Samples were taken under nonstressful conditions. In expt 1, the acute effects of two doses (10 and 20 mg/kg) of the tricyclics clomipramine (CMI), desipramine (DMI) and imipramine (IMI), and the non-specific monoamine oxidase inhibitor (MAOI) phenelzine were studied. Only phenelzine increased plasma corticosterone with the low dose, whereas phenelzine and DMI increased plasma corticosterone with the high doses when measured 30 min after drug administration. In a second experiment, it was observed that after 12 daily doses of the drugs (20 mg/kg), all drugs increased plasma corticosterone at 30 min after the last drug administration. When the circadian pattern of corticosterone was studied in the same experiment, starting on the day after the last drug administration, a significant interaction of drug by time of day was found. Drugs caused changes in the normal levels of plasma corticosterone at certain times and DMI, IMI and phenelzine reduced the number of rats showing the normal corticosterone peak at 1900 hours. No significant effect of drugs on corticosteroid-binding globulin (CBG) was found. In a third experiment, phenelzine and IMI were administered as before, but samples were taken at several times both on the day of the last drug administration and on the following day. The two drugs altered the normal circadian pattern of corticosterone in a somewhat different way, but both caused a reduction of the corticosterone peak at lights off on the day after the last drug administration. The normal relative thymus weight observed in all groups (exp. 2) suggests that the overall biological activity of corticosterone was probably not affected by antidepressants. The present results indicate that most antidepressants are able acutely to activate the PA axis after repeated administration in a similar way or even more-strongly than after the first administration, and that some of these drugs alter normal circadian pattern of corticosterone. No evidence for decreased resting PA activity was found in antidepressant-treated rats.
Fawn-Hooded (FH) rats show central and peripheral abnormalities in serotoninergic functions and have attracted attention as an animal model of some pathologies, including depression and hypertension. In addition, these rats show a reduced growth rate. As the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in both depression and hypertension, and the hypothalamicsomatotrophic (HSM) axis has a major role in growth, these two endocrine axes were characterised in FH rats as compared with outbred Sprague-Dawley (SD) rats in basal conditions. FH rats showed normal serum ACTH and corticosterone concentrations, but reduced serum corticosterone binding capacity. At a central level, normal expression of mRNA for glucocorticoid type II receptors in the hippocampal formation and mRNA for corticotrophin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus were observed in FH rats, whereas expression of mRNA for CRF in the central nucleus of the amygdala was enhanced compared with the expression in SD rats. Serum GH concentrations were normal in FH rats, IGF-I tended to be lower, and mRNA for somatostatin (SRIF) in the periventricular nucleus of the hypothalamus was significantly lower in FH rats than in SD rats. The reduced SRIF gene expression in rats with normal or slightly reduced GH and IGF-I, respectively, might be secondary to a defective central and peripheral response to IGF-I, compatible with the reduced growth of FH rats. The present results suggest that FH rats have abnormalities in both HPA and HSM axes that might be related to some of their physiopathological characteristics.
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