Hypnotic Effect Of Pentobarbital Research Articles

Deletion of GABAA receptor alpha 1 subunit-containing receptors alters responses to ethanol and other anesthetics.

GABA(A) receptors have been implicated in mediating several acute effects of ethanol including anxiolysis, ataxia, sedation/hypnosis, and anticonvulsant activity. Ethanol sensitivity of neurons has been associated with expression of alpha1 subunit-containing receptors. The objective of this study was to determine the contribution of alpha1 subunit containing receptors to ethanol responses in comparison to neurosteroids and other anesthetics using GABA(A) receptor alpha1 subunit knockout mice. Deletion of alpha1 subunit-containing receptors did not alter the anxiolytic, ataxic, anticonvulsant, or hypnotic effects of ethanol or acute functional tolerance to ethanol but did increase sensitivity to the locomotor-stimulating effects of ethanol. The ability of ethanol to potentiate muscimol-stimulated chloride uptake and ethanol clearance was also not altered following alpha1 subunit deletion. The anticonvulsant and hypnotic effects of neurosteroids as well as their potentiating effect on GABA-mediated Cl(-) uptake were unaltered in alpha1(-/-) mice. The hypnotic effect of pentobarbital, etomidate, and midazolam were reduced, whereas the effect of ketamine was enhanced in alpha1(-/-) mice. Thus, GABA(A) receptor alpha1 subunit-containing receptors appear to influence the motor-stimulating effect of ethanol and the sedative/hypnotic effects of some anesthetics, but not ethanol. These receptors do not appear to be necessary for most ethanol responses, suggesting involvement of other GABA(A) receptor subtypes or other targets altogether.

Alteration in hypnotic effect of pentobarbital following repeated agonistic confrontations in mice

We investigated how repeated agonistic confrontations affect the hypnotic effect of pentobarbital (PB) in male mice, using a resident-intruder paradigm. PB concentrations in the cortex, midbrain and brainstem were determined. Agonistic confrontations were terminated after 10 or 20 attack bites, and were repeated for 5 consecutive days. Immediately after the last encounter, PB (55 mg/kg, IP) was administered to both resident and intruder mice. Compared to the control group, intruders exposed to 20 daily attack bites showed a significant prolongation of the latency to sleep and a shortening of the duration of sleeping time. At the stage of induction, no significant difference in brain PB levels was found between the "defeated" and control intruders. At the stage of recovery, however, the "defeated" intruders showed a significantly low level of PB in all brain areas. In contrast, attacking resident mice did not show any significant changes in either the hypnotic effect or regional brain concentration of PB. Because pretreatment with naloxone prior to daily agonistic confrontation antagonized the alteration in PB-induced hypnosis, it seems that endogenous opioid mechanisms may participate in this phenomenon. The present study indicates that susceptibility to a hypnotic drug can be altered by chronic social conflict experience.

Changes in pentobarbital hypnosis and hepatic metabolism in streptozotocin-diabetic mice

The present study deals with the hypnotic effect of pentobarbital (Pento) in relation to its metabolism in hepatic microsomes in streptozotocin (STZ, 170 mg/kg, i.p.) injected mice. Liver weight (mg/10 g body wt.) of STZ-treated mice was larger than that of the controls throughout the experimental period. Although the shortening of sleeping time induced by Pento (60 mg/kg, i.p.) was always observed, Pento-metabolizing enzyme activity (by the method of Kato et al., 1964) increased in mice with diabetes for 2 and 4 weeks but decreased in mice with diabetes for 8 weeks. Induction following phenobarbital (100 mg/kg, s.c.) and inhibition by SKF 525-A (10 mg/kg, i.p.) of hepatic metabolizing enzyme were found in both control and mice with diabetes for 2, 4 and 8 weeks, but these were not definitely correlated to their hepatic Pento-metabolizing enzyme activities. STZ-induced hyperglycemia and shortening of sleeping time by Pento were completely prevented by the pretreatment with nicotinamide (500 mg/kg, i.p.). NPH-insulin injection partially decreased hyperglycemia in STZ-diabetic mice, but sleeping time by Pento was not significantly affected. These results suggest that the hyposensitivity to Pento in STZ-diabetic mice is partially related to an abnormality of metabolism in liver such as the hyperglycemic state.

The effect of thyrotropin releasing hormone on pentobarbital tolerance

The effects of thyrotropin releasing hormone (TRH) on the responses produced by acute and chronic administration of pentobarbital (PB) were investigated in male Swiss Webster mice. Intraperitoneal injection of TRH antagonized the hypothermic and hypnotic effect of PB (75 mg/kg, i.p.). Pentobarbital hypnosis was also antagonized by TRH in mice rendered tolerant to PB by implantation of a pellet (each containing 75 mg of free acid form of the drug) for two days. Injections of TRH (5 mg/kg) once a day or twice a day for two days did not modify the development of tolerance to the hypothermic and hypnotic effect of PB. It is concluded that TRH can modify only the acute responses of PB in naive and PB-tolerant mice, however, in the dosage regimen used it does not affect the processes involved in the genesis of the tolerant state.