Diethylstilbestrol counteracts barbiturate narcosis and hypothermia in male mice.

Treatment with DES one hour prior to pentobarbital injection resulted in diminution of the narcotic sleep and hypothermia usually found after pentobarbital (50 mg/kg 1) injection in male mice. The effect was biphasic: significantly countered relative to saline pretreated controls at low (.001-.10 mg/kg 1) and at high (10-50 mg/kg -1) DES doses only. Giving DES alone did not change core body temperature compared to saline injected controls, at either 25 degrees C or at 33 degrees C. At 33 degrees C, neither PeB narcosis nor body temperature loss was significantly inhibited by DES. Possible cytoplasmic, nonsex differentiated bases for these estrogen effects on barbiturate action in the brain is discussed.

Alterations in mice dopamine receptor characteristics after early exposure to phenobarbital.

The present experiment was designed to study the sensitivity of dopamine (DA) receptors after early (pre- and neonatal) administration of phenobarbital (PhB). These receptors have been implicated in some of the behaviors which are altered by early barbiturate exposure. Pregnant HS mice were exposed to PhB (3 g/kg milled food) from the 9th to the 18th day of gestation. Their offspring were the subjects of the prenatal studies. The neonatal treatment consisted of daily injections of PhB to pups from ages 2 to 21 days (50 mg/kg PhB). Striata of treated animals and controls from both treatments, prenatal (PreB) and neonatal (NeoB) were removed at 22 or 50 days for DA receptor binding assay. Using Scatchard plot analysis of [3H]spiroperidol specific binding, long-term increase from control level in DA receptor number (Bmax) was found in the PreB mice, while NeoB mice had decreased Bmax (P less than 0.001). No differences were found in the respective KD values. In parallel psychopharmacological studies, PreB mice had increased apomorphine-induced climbing behavior response, and in previous studies we showed that NeoB had decreased apomorphine induced-climbing behavior response. The long-term alterations in DA receptor number may possibly mediate the changes in brain sensitivity to barbiturate and alcohol found in our previous studies.

Chronic treatment with haloperidol affect the response of the brain to pentobarbital.

Treatment of mice with haloperidol increased the number of dopamine D2 receptors (Bmax). The animals were given 40 or 50 mg of pentobarbital. Animals treated with haloperidol had a shorter duration of narcosis induced by pentobarbital than the controls, suggesting a decreased sensitivity to pentobarbital which was functional (CNS), since the animals treated with haloperidol had higher levels of pentobarbital in the brain upon awakening than the controls. The results suggest that increased Bmax reduces the sensitivity of the brain to pentobarbital.