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ABSTRACT: Much progress has been made in our understanding of brain regions and specific receptors that are involved in the action of cocaine addiction. Although long-term modifications of mesolimbic reward circuit following cocaine exposure are responsible for cocaine-addicted behaviors, the underlying molecular mechanism at the cellular level is still obscure. Here, we investigated the possible participation of protein kinase Mζ (PKMζ) in synaptic potentiation following cocaine exposure.
Spontaneous and evoked synaptic activity of glutamate synapse in saline- and cocaine-treated rats were examined by preparing acute brain slices and performing whole-cell voltage-clamp recordings from individual dopamine neurons in the ventral tegmental area (VTA). We also assessed the role of PKMζ on the behavioral responses by cocaine conditioned place preference.
Chelerythrine, an inhibitor of PKMζ, reversed the cocaine-induced facilitation of spontaneous synaptic transmission in the VTA. PKMζ inhibition by chelerythrine or myristoylated ζ inhibitory peptide significantly attenuated the cocaine exposure-induced enhancement of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio. Myristoylated ζ inhibitory peptide had no effect on spike timing-dependent long-term potentiation in rats previously injected with saline but remarkably restored spike timing-dependent long-term potentiation in VTA dopamine neurons in slices prepared from rats that received single or multiple cocaine exposure. Western blot analyses showed that both single and five consecutive cocaine injections induced a significant increase in PKMζ level. Furthermore, intracranial infusion of myristoylated ζ inhibitory peptide in the VTA disrupted cocaine conditioned place preference.
Our results suggest that persistent activity of PKMζ is a requisite for cocaine-induced enhancement of synaptic plasticity in the VTA and cocaine conditioned place preference.
Biological psychiatry 12/2011; 71(8):706-13. · 8.93 Impact Factor
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ABSTRACT: Malnutrition and muscle loss are common in bed-ridden elderly nursing home residents. Supplementation of beta-hydroxy-beta-methylbutyrate (HMB) has been shown to prevent muscle loss in several catabolic conditions. The aim of this study was to investigate the effect of HMB supplementation on body composition and protein metabolism in bed-ridden elderly nursing home residents receiving tube feeding. The subjects were randomly assigned to HMB (n=39, 2 g/d) or control group (n=40). Anthropometry measurements, blood sampling, and 24-hr urine collection were performed on the day before and 14 days after the start of the study. A subgroup of subjects (HMB: n=19, control: n=20) continued the study for another 14 days. Changes in body weight and BMI were not significantly different between the groups after 14 or 28 days after controlling for baseline BMI. Blood urea nitrogen significantly decreased in the HMB group, while it remained unchanged in the control group after 14 days. Urinary urea nitrogen excretion significantly decreased in the HMB group, while it showed a trend of increase in the control group after 14 and 28 days, respectively. Changes in blood urea nitrogen and urinary urea nitrogen excretion were significantly different between the groups after controlling for baseline BMI. This study suggested that HMB supplementation for 2-4 weeks could reduce muscle breakdown in bed-ridden elderly nursing home residents receiving tube feeding.
Asia Pacific Journal of Clinical Nutrition 01/2010; 19(2):200-8. · 1.13 Impact Factor
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ABSTRACT: Arginine supplementation has been shown to alleviate endothelial dysfunction and improve exercise performance through increasing nitric oxide production in patients with cardiopulmonary diseases. In addition, arginine supplementation could decrease accumulations of lactate and ammonia, metabolites involved in development of muscular fatigue. The aim of this study was to investigate the effect of short-term arginine supplementation on performance in intermittent anaerobic exercise and the underlying mechanism in well-trained male athletes. Ten elite male college judo athletes participated with a randomized crossover, placebo-controlled design. The subjects consumed 6 g/day arginine (ARG trial) or placebo (CON trial) for 3 days then performed an intermittent anaerobic exercise test on a cycle ergometer. Blood samples were collected before supplementation, before and during exercise and 0, 3, 6, 10, 30 and 60 min after exercise. ARG trial had significantly higher arginine concentrations than CON trial at the same time point before, during and after exercise. In both trials, nitrate and nitrite concentration was significantly higher during and 6 min after exercise comparing to the basal concentration. The increase in nitrate and nitrite concentration during exercise in both trials was parallel to the increase in plasma citrulline concentrations. There was no significant difference between the 2 trials in plasma nitrate and nitrite, lactate and ammonia concentrations and peak and average power in the exercise. The results of this study suggested that short-term arginine supplementation had no effect on nitric oxide production, lactate and ammonia metabolism and performance in intermittent anaerobic exercise in well-trained male athletes.
The Journal of nutritional biochemistry 09/2008; 20(6):462-8. · 4.29 Impact Factor
