Background Perturbations in the function of core circadian clock components such as the Period (Per) family of genes are associated with alcohol use disorder, and disruptions in circadian cycles may contribute to alcohol abuse and relapse. This study tested ethanol consumption, reinforcement, and metabolism in mice containing functional mutations in Per1 and/or Per2 genes on an ethanol-preferring background, C57BL/6J mice. Methods Mice were tested in: (A) free-access intake with ascending concentrations of ethanol (2–16% v/v); (B) conditioned place preference using ethanol (2 g/kg for males; 2.5 g/kg for females) vs. saline injections; (C) recovery of the righting reflex following a 4 g/kg bolus of ethanol; and (D) blood ethanol levels 1 hour after a 2 g/kg bolus of ethanol. Results All Per mutant (mPer) mice showed increased ethanol intake and condition place preference compared to controls. There were also genotypic differences in blood ethanol concentration: in males, only mPer1 mice showed a significantly higher blood ethanol concentration than WT mice, but in females, all mPer mice showed higher blood ethanol levels than WT mice. Conclusions Mutation of either Per1 or Per2, as well as mutations of both genes, increases ethanol intake and reinforcement in an ethanol-preferring mouse model. In addition, this increase in ethanol seeking behavior seems to result both from a change in ethanol metabolism and a change in reward responding to ethanol, but not from any change in sensitivity to ethanol’s sedating effects.

No abstract

The onset of diabetes is characterized by a loss of glucose homeostasis as well as a loss in lean body mass. Recent reports suggest that muscle loss may be fiber type specific and correlated with oxidative capacity (Sandri et al., 2006. PNAS, 103:16260–5). To test this hypothesis a streptozotocin (STZ) ‐treated animal model was used. BALB/c mice were injected with 40 ug/g STZ over the course of 5 days with sham injected controls. Maximal weight loss was observed 5 days post‐injection. Animals were sacrificed at this time and plasma, tibialis anterior (TA) (fast‐twitch), and soleus (SOL) (slow‐twitch), muscles were harvested, weighed and rapidly frozen at −80°C. Plasma glucose levels rose from approximately 150 to 270 mg/dL by day 5. TA muscles decreased in mass from 46 ± 2 to 39 ± 1 mg with no detectable change in SOL weights. Real‐time PCR showed atrogin‐1 mRNA was two‐fold increased in STZ‐treated TA muscles relative to sham‐injected controls but there was no change in SOL expression. Both muscle mass and atrogin‐1 expression show fast‐fiber specific effects under STZ‐treatment that are absent in the more oxidative SOL muscles. These data suggest that oxidative capacity and/or genes controlling oxidative capacity protect against the loss in mass possibly by retarding atrogin‐1 expression.Supported by NIH DK 061184

No abstract

No abstract