NMDA Partial agonist reverses blocking of extinction of aversive memory by GABA(A) agonist in the amygdala

The ability to extinguish aversive memories is of significant clinical interest. The amygdala plays an important role in emotional conditioning and its experimental extinction. It has been suggested that gamma-aminobutyric acid (GABA) agonists retard extinction and that consolidation of extinction involves N-methyl-D-aspartate receptor (NMDAR)-mediated plasticity. The aim was to further explore the interaction between GABA and NMDA in the amygdala in consolidation of experimental extinction in the rat. To that end conditioned taste aversion (CTA) was used. In CTA, the amygdala has been reported to subserve both acquisition and extinction. The GABA(A) receptor agonist, muscimol, administered into the amygdala immediately after the first extinction session, caused lasting disruption of extinction of CTA for at least 2 weeks. However, the administration of GABA(A) receptor antagonists had no effect on extinction kinetics. Microinfusing the partial NMDA agonist D-cycloserine together with or after muscimol infusion reversed the blocking effects of muscimol. These findings could bear relevance to the potential involvement of extinction abnormalities in behavioral disorders, and their amelioration.