14, 15 5‐HT 7 receptor is located in the supra‐chiasmatic nucleus of the hypothalamus, where it is intensely involved in circadian rhythm of animal activity. 12 The 5‐HT 7 receptor, the most recently identified member of the 5‐HT receptor family, 13 has been shown to be involved in several functions modulated by the 5‐HT system such as circadian rhythms. Several physiological functions, such as anxiety/affect or circadian rhythms/sleep, are influenced by 5‐HT system. Previous studies have shown that both 96 hours and 72 hours of REM SD reduce hippocampal neurogenesis of adult rats 9, 10 and because neuroplasticity deficits can be associated to BD, 11 the SD model might be more suitable in understanding neurobiological characteristics of mania and for screening new drugs. We suggest that SD should be investigated more deeply, particularly for its predictive validity, for the following reasons. Nonetheless, even if SD is a triggering factor of manic episodes in BD patients, 8 SD is less studied in the view of mania modeling. ![]() 4, 5 Another relevant model of mania is the rapid eye movement (REM) sleep deprivation (SD) model, firstly proposed by Gessa et al., 7 that produces a transient episode of hyperactivity and insomnia, major clinical symptoms of manic episodes. 5 proposed that animals chronically treated with ACTH can be a useful animal model of TCA treatment‐resistant depression. ![]() 3, 4 Remarkably, similar results are obtained after repeated electroconvulsive seizures and treatment with the dual norepinephrine and dopamine reuptake inhibitor buproprion. 3 were the first to report that chronically administered ACTH (100 μg/d, s.c.), leading to sustained increase in plasmatic corticosterone, counteracts the decrease in the immobility time caused by classical antidepressants including the TCA imipramine, desipramine and the dual serotonin and noradrenaline reuptake inhibitor milnacipran. Actually, the forced swimming test (FST) and amphetamine‐induced hyperactivity test are the most popular paradigms to screen new antidepressant and antimanic candidates, respectively. 1 Ideally, animal models of mental disorders should have construct, face, and predictive validity to identify therapeutic interventions. ![]() Accordingly, developing new therapies is an urgent need. Up to date available treatments, that is, mood stabilizers and antipsychotic drugs, remain unsatisfactory because of their partial therapeutic efficacy and their delayed action. It affects millions of people worldwide, with a lifetime prevalence of 1% to 5% making BD a major concern for public health. Bipolar disorder (BD) is a severe brain disorder characterized by repeated alternation of mania, depression, and euthymia.
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