Role of GABA in memory and anxiety

Abstract

This review assesses the parallel literature on the role of gamma‐aminobutyric acid (GABA) in memory and anxiety. We review historical and new data from both animal and human experimentation which have helped define the key role for this transmitter in both these mental states. By exploring the overlap in these conditions in terms of pharmacology, brain circuitry, and clinical phenomenology, we begin to develop a theory that the two conditions are intrinsically interrelated. The role of GABAergic agents in dissecting out and demonstrating this interrelationship and in pointing the way to future research is discussed. Depression and Anxiety 4:100–110, 1996/1997.© 1997 Wiley‐Liss, Inc.

Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory

“…Also, the enhancing effects of PLZ in CMIA were probably not due to its anxiolytic properties. Typically, anxiolytic drugs impair memory, including inhibitory avoidance retention, and anxiogenic drugs enhance memory (Kalueff and Nutt 1996). Therefore, based on its anxiolytic properties, PLZ would be expected to impair avoidance retention.…”

“…In contrast, evidence suggests that the GABAergic system down-regulates memory storage. Activation of GABAergic receptors impairs memory, while inhibition of these receptors tends to enhance memory (Decker and McGaugh 1991;Izquierdo and Medina 1993;Kalueff and Nutt 1996).…”

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

“…Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and ameliorate GABA deficits in patients with mood disorders (Krystal et al, 2002). GABA receptors, including GABA A receptors and GABA B receptors, have been generally considered as the targets for treatment of mental illness (Kalueff and Nutt, 1996). However, drugs used for such treatment have side effects (Johnston, 1996;Tsang and Xue, 2004).…”

Glutamate and cortisol—a critical confluence in PTSD?

“…We have shown in rats that lorazepam, a benzodiazepine agonist, abolishes phospho-acetylation of histone H3 in stress exposure (Papadopoulos, Chandramohan, Droste, Collins, Nutt and Reul, unpublished), which may explain why being on another GABA-A agonistic drug, alcohol, during the trauma reduces PTSD incidence (McFarlene, 2000). It also helps explain the old human data that the benzodiazepine receptor inverse agonist FG7142, and other GABA-A receptor antagonistic drugs produced severe anxiety (Nutt and Ballenger, 2003) and a PTSD-like state in humans (Kalueff and Nutt, 1996) because in rodents we found that FG7142 enhanced histone H3 phospho-acetylation in dentate neurons (Papadopoulos, et al, unpublished).…”