Depressive behavior and selective downregulation of serotonin receptor expression after early-life seizures: Reversal by environmental enrichment

Abstract

Depression is the most common psychiatric comorbidity in epilepsy. To better understand the contribution of seizures versus environment to depression in epilepsy, we investigated differential gene expression using microarray and quantitative RT-PCR, and depressive behavior, in the Porsolt forced swim test in juvenile rats reared in different environments after kainic acid (KA)-induced seizures. We selected for genes significantly down-regulated by KA seizures and upregulated by environmental enrichment. This common gene selection process yielded one known gene involved in mood and affect: serotonin receptor 5B. The changes in serotonin receptor gene expression were paralleled by decreased mobility in the forced swim tests; depressive behavior exhibited after seizures was no longer evident in rats reared in environmental enrichment. Our results suggest that seizures lead to increased susceptibility to depression through transcriptional regulation while environment, in turn, can interact with gene expression to influence the behavioral outcome of epilepsy.

A final common pathway for depression? Progress toward a general conceptual framework

“…For the first are the findings that enhancement of aminergic neurotransmission by blockade of inhibitory α 2 - (Zebrowska-Lupina, 1980;Nyberg et al, 2006) and 5HT1A (Ballesteros and Callado, 2004) receptors can hasten and enhance antidepressant action in both animal models and people. Furthermore, physiological stimulation of the positive network by exercise and environmental enrichment are known to have therapeutic effects in depression (Harris et al, 2006;Koh et al, 2007). In support of the second are the findings that a) localized deep brain stimulation blockade of the subgenual anterior cingulate stress-node produces immediate relief and long term recovery from depression Mayberg et al (2005); b) antidepressants increase expression of GR and MR in the hippocampus, which would have the effect of dampening stress circuit activation (Het and Wolf, 2007); c) antidepressants infused into the CeA have been shown to reverse the immobility in the repeated forced swim test (Duncan et al, 1986); and finally, d) suppression of stress circuit activity by clonidine infusion in the LC and systemic corticosterone produce rapid antidepressant effects.…”

Phenomenology and Therapy of Affective Disorders in Epilepsia

“…Длительное применение фено-барбитала и других барбитуратов наиболее часто приво-дит к мнестико-интеллектуальному снижению, депрессии и даже к суицидальной готовности у больных эпилепсией, что было показано и российскими, и зарубежными иссле-дователями [6,9,27]. По мнению ряда авторов, назначе-ние противоэпилептических препаратов с ГАМК-ерги-ческими свойствами (вигабатрина и тиагабина, а также габапентина) чревато седацией и чаще вызывает депрес-сию [27,28]. Топирамат оказывает тимолептическое дей-ствие, но в то же время может вызывать тревожность, раздражительность и беспокойство, а в отдельных случа-ях (в основном при быстрой титрации или начале приема с высоких доз) -психозы [28].…”

The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

“…Although data favors the hypothesis that epilepsy and its behavioral comorbidities have a common underlying mechanism, and that morphological, biochemical, and behavioral changes caused by one disorder may provoke another, the exact pathogenesis of behavioral comorbidities in epilepsy remains obscure, and there is a lack of standard screening and treatment approaches (Ott et al, 2003). Over the last decade, several laboratories have validated animal models of comorbidity, such as depression and ADHD (Koh et al, 2007;Ma and Leung, 2004;Mazarati et al, 2008;Pineda et al, 2010;. We have recently reported on strain-related behavioral differences, using the KAinduced epilepsy model, which is also considered a model of depression comorbidity (Tchekalarova et al, 2010).…”