Enhancement of ethanol-induced sedation and hypothermia by centrally administered neurotensin, β-endorphin and bombesin

Intracisternal administration of three endogenous neuropeptides (neurotensin, β-endorphin, or bombesin) potentiated the duration of sedation induced by a fixed dose of ethanol (5.2 g/kg) in mice. The minimally effective dose of each peptide that enhanced ethanol-induced sedation was: neurotensin, 0.18 nmoles; β-endorphin, 1.79 nmoles; and bombesin, 0.06 nmoles. The enhancement of ethanol-induced sedation was correlated with the potentiation of ethanol-induced hypothermia for all three peptides. None of the neuropeptides studied significantly altered blood or brain ethanol concentrations, suggesting that the observed effects were not due to differences in ethanol metabolism

Modification of pentobarbital-induced sedation by natural and synthetic peptides

The effect of intraperitoneal (i.p.) and intracisternal (i.e.) injection of various endogenous peptides and related analogues on the sedation induced by a fixed intraperitoneal dose of sodium pentobarbital in mice was examined. Several peptides were found to antagonize the effects of pentobarbital while one (neurotensin) markedly potentiated them. Certain peptides were active only after intracisternal injection, while others were effective by either route of administration. However, peptides active after intraperitoneal administration were always active after intracisternal administration. Thyrotropin-releasing hormone was the most effective antagonist and was active by both routes. Neurotensin was the most potent potentiator but was active only after central administration. Although few general structural requirements for the analeptic activity of peptides are discernable, it appears that such activity is mediated by the central nervous system

Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.

Item does not contain fulltextLesch-Nyhan disease, a neurogenetic disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase, is associated with a prominent loss of striatal dopamine. The current studies address the hypothesis that oxidant stress causes damage or dysfunction of nigrostriatal dopamine neurons in a knockout mouse model of the disease, by assessing several markers of oxidative damage and free radical scavenging systems. Some of these measures provided evidence for an increase in oxidative stress in the mutant mice (aconitase activity, oxidized glutathione, and lipid peroxides), but others did not (superoxide dismutase, protein thiol content, carbonyl protein content, total glutathione, glutathione peroxidase, catalase, and thiobarbituric reducing substances). Immunolocalization of heme-oxygenase 1 provided no evidence for oxidative stress restricted to specific elements of the striatum or midbrain in the mutants. Striatal dopamine systems of the mutant mice were more vulnerable to a challenge with the neurotoxin 6-hydroxydopamine, but they were not protected by cross-breeding the mutants with transgenic mice over-expressing superoxide dismutase. Overall, these data provide evidence for increased oxidative stress, but the failure to protect the knockout mice by over-expressing SOD1 argues that oxidative stress is not the sole process responsible for the loss of striatal dopamine