Possible Interaction: Antidepressive Agents and Gamma-Aminobutyric Acid

“Finally, we discuss the connections between serotonergic and GABAergic neurotransmission, and show that two serotonin-focused antidepressants – the selective serotonin-reuptake inhibitor fluoxetine and the multimodal antidepressant vortioxetine – modulate GABA neurotransmission in opposing ways, despite both being effective MDD treatments.”

“Our data in combination with previous ones from other laboratories suggest that antidepressants suppress the activity of presynaptic 5-hydroxytryptamine3 receptors on GABA neurons, resulting in the reduction of GABA release.”

“We reviewed possible involvement of gamma-aminobutyric acid (GABA)B receptors in action of antidepressants.”

“Anxiogenic agents augment norepinephrine activity, some anxiolytics increase serotonin neurotransmission while benzodiazepines and antidepressants influence catecholamine, indoleamine and gamma-aminobutyric acid turnover in infrahuman subjects.”

“Background: Previous studies have demonstrated that antidepressant medication and electroconvulsive therapy increase occipital cortical γ-aminobutyric acid (GABA) in major depressive disorder (MDD), but a small pilot study failed to show a similar effect of cognitive-behavioral therapy (CBT) on occipital GABA.”

“Since recent neuroimaging studies have demonstrated that antidepressants modulate GABA levels, additional experiments were performed to examine the levels of GAD in eight depressed subjects treated with antidepressant medications.”

“Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), while it … partial onset seizures as well as for fibromyalgia that is commonly comorbid with depressive disorders.(Pae et al., 2008) Antidepressants … GABA levels but also ameliorate … (Lodge and Li, 2008).”

“In support of these observations, we review data from animal models of epilepsy showing that decreased activity of serotonin, norepinephrine, dopamine, and GABA facilitate the kindling process of seizure foci, worsen seizure frequency and severity, and are reversed or blocked by antidepressant drugs.”

“We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity.”

“A widely used antidepressant drug , however, increased GABA co-release.”

“Since antidepressants have been reported to inhibit GABA uptake, we examined those effects on mouse BGT1 (mBGT1) in comparison with other mouse GAT (mGAT) subtypes in the heterologously expressed cell cultures.”