Rats on a chronic intermittent ethanol (CIE) regimen showed a persistent reduction in seizure threshold to the convulsant drug pentylenetetrazol (PTZ). CIE rats were given ethanol by intubation on an alternate day schedule and tested at selected intervals for seizure threshold with PTZ. A significant reduction in seizure threshold, a sign of withdrawal, was observed 20 hr after the first dose. The severity of withdrawal intensified on repetition of the ethanol administration and depression-hyperexcitability cycle, with the seizure threshold reaching a maximum decrease after 12 doses and remaining reduced up to 60 doses. The reduction in seizure threshold persisted for at least 40 days of no alcohol following the 60th dose. The long-lasting decrease in seizure threshold following CIE treatment resembled the "kindling" phenomenon produced by chronic administration of PTZ (25 mg/kg, 3 times/week). The CIE rats developed, in addition, a tolerance to the anticonvulsant action of ethanol, which occurred well after the decrease in PTZ seizure threshold, and a tolerance to the hypothermic effect of ethanol, which developed rapidly. PTZ kindled rats that had never been exposed to ethanol also exhibited tolerance to the hypothermic effect of ethanol. We propose that kindling contributes to the mechanism of the development of dependence on central nervous system depressants like benzodiazepines, barbiturates, and alcohol, drugs that act on the gamma-aminobutyric acid-A receptor chloride ion channel complex. Repeated episodes of depression and withdrawal hyperexcitability are postulated to produce kindling during the repeated withdrawal episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

No abstract

No abstract

Long lasting effects of perinatal ethanol exposure were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet ad libitum or pair-fed the isocaloric control diet during gestation weeks 2 and 3 or during postnatal week 1. Fetal exposure to ethanol reduced body weight of pups at birth unless the ethanol diet was supplemented with casein; neonatal exposure to the ethanol or pair-fed diets, casein supplemented or not, reduced pup weights until day 21 postnatally when weights of all fetally or neonatally exposed pups were normal. Between 52 and 120 days of age females were tested for pituitary-adrenal and temperature responses to a challenge dose of ethanol. Prenatally ethanol-exposed rats showed significantly higher plasma corticosterone titers and developed a greater hypothermia in response to an intraperitoneal injection of ethanol (0.75--1.5 g/kg) than did pair-fed controls. Similar responses enhancement did not occur in the postnatally ethanol-exposed rats. Temporal patterns of blood ethanol levels after an intraperitoneal injection of ethanol (1.5 g/kg) were similar in prenatally ethanol-exposed females and their pair-fed controls. The data indicate that exposure to ethanol in utero exerts persistent effects on the offspring, rendering them more responsive to the hypothermic and pituitary-adrenal activating effects of alcohol as adults.

No abstract

No abstract

Injection of microquantities of morphine into two sites in the hypo-thalamus was found to depress the release of radioiodine from the thyroid gland of rats. These sites lay in the supraoptic or the supramammillary region close to the midline. Injection of 0.9 % NaCl into the supraoptic area caused accelerated thyroid activity. These responses to morphine may represent a dual action of the drug: stimulation of neurons in the caudal hypothalamus that inhibit thyroid stimulating hormone release and depression of neurons in the rostral region that normally activate the pituitary-thyroid axis.