Norio Kokka

Long-term effects of fetal ethanol exposure on pituitary-adrenal response to stress ☆

Pregnant female rats were fed either a 5.0-5.5% w/v ethanol-containing liquid diet ad lib or pair-fed the isocaloric control diet during gestation weeks 2 and 3. At 75-105 days of age, female offspring of the ethanol-treated dams showed significantly greater corticosterone responses than pair-fed- or normally-derived offspring to the stress of cardiac puncture or of noise and shaking, while pituitary-adrenal responses to exposure to a novel environment, cold or 2-3 days of fasting were normal. Adrenal sensitivity to ACTH in dexamethasone-suppressed adult offspring was unaffected by the prenatal treatment. The results demonstrate that fetal ethanol exposure enhances adult pituitary-adrenal responses to certain stressors, including alcohol as demonstrated previously, and suggest that the long-term effects may be mediated by developmental actions of alcohol on central neural mechanisms involved in the regulation of this neuroendocrine system.

Sex differences in sensitivity to pentylenetetrazol but not in GABAA receptor binding

Female rats have a higher threshold than males for seizures induced by the convulsant pentylenetetrazol, a GABAA receptor-chloride channel complex blocker. No sex difference was observed for the anticonvulsant activities of ethanol or diazepam to protect against pentylenetetrazol seizures. Ovariectomy reduces the pentylenetetrazol seizure threshold of females to that of males. In contrast, females have a lower threshold than males to electroshock seizures. Pentylenetetrazol receptors were compared in males and females and gonadectomized animals by binding of several radioligands to the GABAA receptor complex. No differences were found for these four groups of animals in the binding of [3H]flunitrazepam to the benzodiazepine sites and [35S]t-butyl bicyclophosphorothionate ([35S]TBPS) to the chloride channel/convulsant sites in membrane homogenates, nor for allosteric modulation of binding by GABA, the steroid anesthetic alphaxalone, or the benzodiazepine Ro 5-4864. In tissue section autoradiography, no difference was observed for these same assays nor for the binding of [3H]muscimol in the presence and absence of alphaxalone in several major regions. We conclude that circulating female sex hormones, possibly neurosteroid metabolites of progesterone, known to interact directly with the GABAA receptor complex, are involved in the sex differences in pentylenetetrazol seizure susceptibility.

Electrical stimulation and lesions of the hypothalamus in alloxan diabetic rabbits

Summary The effects of hypothalamic stimulation and lesions were studied in alloxan diabetic rabbits. Electrical stimulation of the anterior hypothalamic area increased the severity of diabetes, by further elevation of blood glucose, whereas electrolytic lesions in this area in some animals, produced a marked increase in the response to insulin. Stimulation of the preoptic, supraoptic, posterior and mammillary areas of the hypothalamus did not alter blood glucose levels. The response to insulin in diabetics with posterior hypothalamic lesions was not different from diabetics without lesions. Insulin sensitivity was compared in normal and adrenal demedullated rabbits and no difference was noted. The results indicate that the anterior hypothalamus in the rabbit plays a part in the regulation of blood glucose which is independent of the sympathetico-adrenal system; it more likely involves an alteration of one or more anterior pituitary secretions of ‘diabetogenic’ hormones.