ABSTRACT
The role of gamma-amino butyric acid [GABA] in mood disorders and its interaction with serotonin [5-HT] and norepinephrine [NE] systems is worthy of further study. Many studies reported that plasma GABA levels are relatively reduced in depressed patients. The present study investigated the alteration of GABA content by long-term antidepressant treatment with either paroxetine as one of the selective serotonin r-euptake inhibitors [SSRIs] or venlafaxine as a serotonin-norepinephrine re-uptake inhibitor [SNRI] in the frontal cortex [F.Cx] [as a brain region crucial for the control of emotion and cognition] obtained from male mice exposed to chronic mild stress[CMS]-induced anhedonia. The long term behavioral changes of the CMS without and with antidepressant treatment were also tested using the forced swimming test [FST]. The results demonstrated the reversal of CMS-induced anhedonia after 3 weeks i.p. administration of 1 and 8 mg/kg/day paroxetine and venlafaxine, respectively. Furthermore, venlafaxine seems to be more efficacious than paroxetine in long-term behavioral changes recorded by the FST. Additionally, there was a significant [p<0.001] increase in the GABA content of the F.Cx of mice exposed to CMSinduced anhedonia. The present study suggested that GABA levels may be decreased in an animal model of depression and its reversal together with the behavior improvement by either paroxetine or venlafaxine could support the hypothesis that modification in GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders