Extracellular levels of serotonin and GABA in the hippocampus after chronic mild stress in rats. A microdialysis study in an animal model of depression

Abstract: One of the most established hypotheses of depression focuses on alteration of the serotonergic (5-HT) function. Recent evidence suggests that serotonergic involvement in depression may be modulated by the action of gamma-hydroxybutyric acid (GABA). Furthermore, altered GABAergic function is also evident in depressed patients and in animal models of depression. Disturbed sleep is characteristic of patients with mood disorders. The most pronounced changes of the 5-HT firing activity occur during sleep. Hence, the present paper reports a study on simultaneously measurement of hippocampal levels of serotonin and GABA during waking and sleep in the chronic mild stress (CMS) animal model of depression. The neurotransmitter findings are accompanied by depression-like symptoms (e.g. sleep alterations and reduced sucrose intake, a putative indicator of anhedonia in rodents). Our results show that animals exposed to CMS had lower hippocampal GABA levels compared to controls. In addition, after CMS there was a lack of 5-HT stage-dependency. A subgroup (five out of eight animals) showed a consistent increase in 5-HT levels in slow wave sleep and REM sleep. We also observed that this increase occurred in those animals regarded as most anhedonic (lowest intake of sucrose solution). Moreover, REM sleep was positively correlated with anhedonia. No interaction between 5-HT and GABA was found in the hippocampus. The data suggest that both GABAergic and serotonergic systems may be simultaneously but independently involved in depression. The alteration in 5-HT function may represent a link between depression-like behaviour and sleep abnormalities found in depressed patients. [Copyright &y& Elsevier]