On the role of endogenous GABA in the forced swimming test in rats

Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1

“…In our present study, we found a significantly reduced immobility time for GAT1 À/À mice in both tests. These behavioral effects are similar to those that we and other investigators have observed for wild-type animals treated with antidepressant drugs, such as amitriptyline, imipramine, and fluoxetine ( Figure 1b) (BilkeiGorzo et al, 2002;Borsini et al, 1988;Porsolt et al, 1977a). Fluoxetine, a selective serotonin reuptake inhibitor, has high affinity for the 5-HTT.…”

“…'behavioral despair' in which animals no longer escape, is thought to be related to depression, and drugs with antidepressant activity reduce the time that the animals remain immobile (Bilkei-Gorzo et al, 2002;Borsini et al, 1988;Porsolt et al, 1977a). In our present study, we found a significantly reduced immobility time for GAT1 À/À mice in both tests.…”

Increased Vulnerability to Depressive-Like Behavior of Mice with Decreased Expression of VGLUT1

“…Several spectroscopy studies have shown decreased GABA levels in the cerebral cortex of depressed patients (3-7) associated with the mood state (5). Moreover, decreased glial EAAT1 has been observed in cortical postmortem tissue of patients who had suffered major depression (9) and preclinical studies have also linked decreased GABA levels to helplessness in the forced swimming test (27). Since glutamate is required for the major neuronal GABA synthesis pathway (28), alterations in glutamate release and/or glial reuptake would be expected to affect GABAergic neurotransmission.…”

GABAergic dysfunction in mood disorders

“…This reaction is sensitive to tricyclic antidepressants and electroconvulsive shock therapy (ECST), but not to anxiolytic or major GABA plasma levels kin 40% of depressed, manic, and euthymic mood disorder patients 98,[116][117][118][119][120] 2 in depressed patients 132 GABA enzyme activities kplatelet GABA-T and plasma GAD activities in unipolar and bipolar patients 127,128 Post-mortem studies kGAD activity 130 and mGABA A receptors 141 in the brain of depressed patients k GABA cortical levels with m depression severity in mood disorder patients 151 kexpression of GAD 65 and GAD 67 in prefrontal cortex 148 [141][142][143][144][145][146] Neuroimaging studies kGABA A receptors in the sensory motor cortex of mood disorder patients with akinetic catatonia 152 kGABA occipital cortex levels in depressed patients 153 Neuroendocrine studies (GH response to baclofen ) k in depressed patients 163,164 m in manic patients 161 2 in depressed patients, 162,165,166 Genetic studies Bipolar disorder: association with GABA A receptor a5 (GABRA5) 178 and a3 subunits (GABRA3) 180 possible linkage of GABRA5 and GABA A receptor b1 subunit (GABRB1) loci 181 no association with GABRA1, 179,181,186,188 70,71 Reduced GABA levels in rat nucleus accumbens, brain stem, and cortex have been reported after a session of forced swimming test. 72 Also, muscimol, a GABA agonist, reduced the immobility, ...…”