Additive effect of BLA GABAA receptor mechanism and (+)-MK-801 on memory retention deficit, an isobologram analysis

Abstract

There is a near correlation between N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptors in the modulation of learning and memory in the basolateral amygdala (BLA). In this study, we investigated the involvement of GABAA receptors in the BLA in amnesia induced by (+)-MK-801, a noncompetitive antagonist of NMDA receptors, in male Wistar rats. After guide cannulae were bilaterally placed in the BLA, animals were trained in a step-through type passive avoidance task and then tested 24h after training to measure memory retrieval and locomotor activity. Post-training intra-BLA microinjection of (+)-MK-801 (0.5μg/rat) and GABAA receptor agonists (muscimol at doses 0.05 and 0.1μg/rat) or antagonist (bicuculline at doses 0.05 and 0.1μg/rat) decreased step-through latency during retrieval but did not alter locomotor activity. Results also showed that a subthreshold dose of muscimol (0.025μg/rat) potentiated impairment induced by (+)-MK-801, whereas bicuculline (0.025μg/rat) restored it. Furthermore, the highest dose of muscimol (0.5μg/rat) increased locomotor activity induced by (+)-MK-801. Isobologram analysis showed that there was an additive but not synergistic effect between muscimol and (+)-MK-801 on memory retention deficits in the BLA. In conclusion, muscimol and bicuculline decreased retention of memory formation in the BLA, and GABAA receptors in the BLA may be involved in the additive effect on (+)-MK-801-induced memory retention deficits.