Progress in biochemical pharmacology最新文献

The effects of bilateral electrolytic hippocampal lesions on voluntary ethanol selection were examined in five groups (n = 10 each) of male mice. Mice sustained lesions in the dorsal hippocampus (DH), central hippocampus (CH), ventral hippocampus (VH), were sham-operated (SH) or left unoperated. CH mice exhibited a preference for ethanol compared with all other groups (p less than 0.01). In a second experiment, ethanol preference threshold and 24-hour drinking patterns were examined in CH and SH mice. These data revealed a higher preference threshold in CH mice, but not difference in drinking activity periods compared with controls. The central hippocampal area may be important in ethanol ingestive behavior in mice.

Growth hormone (GH) regulates not only somatic growth but also carbohydrate, protein and lipid metabolism. Altered secretory states resulting from alcohol use could have pathogenetic significance. The pattern of spontaneous GH secretion in man is reviewed and previously published human studies on ethanol and GH examined to develop a coherent formulation of the nature of ethanol effects on GH secretion. The weight of the evidence suggests that ethanol suppresses GH secretion. Studies using the rat indicates that the dose-response relationship is of a threshold nature, with doses of 3 g/kg or greater abolishing spontaneous secretion. The possible role of diminished GH secretion in the pathogenesis of the fetal alcohol syndrome is discussed.

Marihuana and alcohol have been reported to exert a wide range of effects on reproductive functions in man and laboratory animals. Decreased testosterone levels, suppression of pituitary gonadotropin release, impaired fertility and sexual dysfunction have been observed in adult males exposed to either of these substances. The present studies examined the effects of perinatal exposure to ETOH and THC alone or in combination on the development or reproductive functions in mice. Testes weights and plasma testosterone levels were reduced in adult males perinatally exposed to these substances, alone or in combination. Seminal vesicle weights were reduced only in the THC-exposed mice, while kidney weights were decreased by either ETOH or THC exposure. In ETOH plus THC-exposed animals, plasma LH was reduced while FSH levels were increased. In response to castration, gonadotropin levels were elevated in mice perinatally exposed to THC. In vitro responsiveness to gonadotropin stimulation, as indicated by testosterone production by decapsulated testes, was significantly inhibited in tissue obtained from ETOH-exposed males. Although no simple interactions were observed, it is evident that THC and ETOH, either alone or in combination, can affect the development of male reproductive functions in mice.

The purpose of this study was to examine, in the pregnant ewe and its fetus, some of the physiological consequences of acute and chronic ethanol exposure. Ethanol was infused intravenously (2 g/kg/day over 2 h) to pregnant ewes from day 100 of pregnancy to term. Control animals received isocaloric infusions of 5% dextrose. Animals were pair-fed and allowed water ad lib. Maternal (n = 5) systolic, diastolic, and mean blood pressures and heart rate rose significantly by 1 h after starting ethanol, whereas fetal (n = 4) blood pressure and heart rate did not change during ethanol infusion. Maternal ethanol infusion produced a significant rise (p less than 0.01) in both fetal (n = 8) and maternal (n = 10) plasma cortisol levels. Peak blood ethanol concentration was significantly higher in the ewe (240 +/- 6 mg.dl-1, n = 7) than in the fetus (190 +/- 9 mg.dl-1, n = 6) at the end of the 2-hour infusion. Maternal rate of elimination after ethanol infusion was terminated was 40 mg.dl-1 per hour, while fetal elimination was 10 mg.dl-1 per hour. Body weights and crown-rump lengths of fetuses from 0.82 to 1.0 gestation were significantly less in ethanol-treated animals than in age-matched control animals. Fetal plasma thyroxine and triiodothyronine increments following thyrotrophin-releasing hormone administration were significantly less in alcohol-treated than in control animals. Thus, chronic exposure to ethanol during the latter part of gestation impaired fetal growth and altered fetal endocrine function in these animals.

While the actions of alcohol on endocrine function in adults are well-documented, the effects of fetal exposure to alcohol on neuroendocrine function in neonates and adults are only beginning to be investigated. Recent reports are reviewed which demonstrate effects of fetal alcohol exposure on pituitary-adrenal function, GH secretion, thyroxine levels and sexual differentiation in newborn rodents. Our studies of the long-term effects of fetal and early postnatal exposure to alcohol on pituitary-adrenal and body temperature responses to a challenge dose of ethanol in adult rats are described. Both responses are enhanced in prenatally, but not in postnatally exposed rats, indicating that the effects of fetal alcohol exposure on physiological systems, such as the endocrine and thermoregulatory systems, persist to adulthood. Based on apparent similarities in the somatic and cerebral deficits which occur following fetal alcohol exposure and neonatal corticosteroid treatment, a hypothesis is developed for the role of alcohol-induced activation of the HPA axis during gestation in the adverse effects of fetal alcohol exposure.