No abstract

NTR 1756.

The preservation of 3 predictors in models derived from variable populations and the fairly consistent predictive properties of most models in 2 distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted because predictive performances are below the desired level.

No abstract

Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY-and galanin-like immunoreactivities (LI) while NPY-and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.