Previous research shows that ketamine significantly alters cardiac signal regulation in rhesus monkeys, however relatively little is known about the mechanism for this effect. In the study reported here the relative contributions of NMDA receptor activation on cardiac signal dynamics were determined by administering a specific NMDA antagonist, MK801, to rhesus monkeys. The general effects of sedation were assessed by measuring cardiac response to lorazepam, a sedative drug without direct NMDA receptor activity.
View Article and Find Full Text PDFThe short allelic variant of the serotonin transporter protein promoter polymorphism (5HTTLPR) appears to influence binge drinking in college students. Both monoamine oxidase type A (MAOA) and the serotonin transporter protein are involved in the processing of serotonin, and allelic variants are both associated with differences in the efficiency of expression. We hypothesized that a significant gene x gene interaction would further stratify the risk of binge drinking in this population.
View Article and Find Full Text PDFNon-human primates are widely used in research, yet relatively few studies have addressed potential pharmacokinetic differences between males and females. The present study examined the relationship between total body water, sex, age, and weight in the rhesus macaque (Macaca mulatta). Ethanol-naïve, adolescent rhesus macaques (n = 119) were administered ethanol (males, 2.
View Article and Find Full Text PDFAims And Methods: In the present study, differences in alcohol consumption behaviour associated with the presence of the short variant (S) of the serotonin transporter promoter polymorphism (5-HTTLPR) was investigated in a Caucasian subset (n = 204) of 268 college students.
Results: Students who were homozygous for the S allele were more likely to engage in binge-drinking behaviour, drank more alcohol per occasion, and reported drinking to get drunk more often.
Conclusions: In this Caucasian sample, the 5-HTTLPR strongly influences alcohol consumption in late pubescence.
Calpain inhibitors prevent proteolytic degradation of cellular proteins due to activation of calcium-activated cysteine proteases (calpains). As a class, they show promising cytoprotective activity in a variety of disorders where the final common pathway is increased intracellular concentrations of calcium, activation of calpain-mediated protein degradation, and subsequent cell death. These disorders include cerebral stroke, cerebral and spinal cord trauma, and myocardial infarction.
View Article and Find Full Text PDFNeurotoxicology
September 2002
Oxidative stress plays an important role in many neurodegenerative conditions including Alzheimer's disease and Parkinson's disease. 4-Hydroxynonenal (HNE), a lipid-soluble aldehydic product of membrane peroxidation, has been known to decrease neuronal survival by impairing Na+, K+, and -ATPase activity. HNE also increases neuronal vulnerability to excitotoxic injury and disrupts homeostasis by activating proteases which mediate the destruction of cellular protein and structure.
View Article and Find Full Text PDFSerotonin type-3 (5-HT3) receptors are cation permeable membrane receptors which are involved in modulation of calcium entry in neuronal cells. Along with other ion-channels such as the N-methyl-D-aspartate receptor, it appears to be a target for the actions of ethanol and has been the focus of considerable work in this regard. Since in animals, ethanol exposure results in elevations of corticosteroids in both acute and chronic conditions, we studied the effects of both ethanol and corticosteroid exposure on 5-HT3 gene expression in an in situ pheochromocytoma-12 (PC12) cell model.
View Article and Find Full Text PDFCalpains (EC 3.4.22.
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