The effect of GABA-B receptors in the basolateral amygdala on passive avoidance memory impairment induced by MK-801 in rats.

MK-801 (dizocilpine) is a potent non-competitive N-methyl-[D]-aspartate (NMDA) receptor antagonist that affects cognitive function, learning, and memory. As we know, NMDA receptors are significantly involved in memory function, as well as GABA (Gamma-Aminobutyric acid) receptors. In this study, we aimed to discover the effect of GABA-B receptors in the basolateral amygdala (BLA) on MK-801-induced memory impairment. We used 160 male Wistar rats. The shuttle box was used to evaluate passive avoidance memory and locomotion apparatus was used to evaluate locomotor activity. MK-801 (0.125, 0.25, and 0.5 µg/rat), baclofen (GABA-B agonist, 0.0001, 0.001, and 0.01 µg/rat) and phaclofen (GABA-B antagonist, 0.0001, 0.001, and 0.01 µg/rat) were injected intra-BLA, after the training. The results showed that MK-801 at the dose of 0.5 µg/rat, baclofen at the doses of 0.001 and 0.01 µg/rat, and phaclofen at the doses of 0.001 and 0.01 µg/rat, impaired passive avoidance memory. Locomotor activity did not alter in all groups. Furthermore, the subthreshold dose of both baclofen (0.0001 µg/rat) and phaclofen (0.0001 µg/rat) restored the impairment effect of MK-801 (0.5 µg/rat) on memory. Also, both baclofen (0.0001 µg/rat) potentiated the impairment effect of MK-801 (0.125 µg/rat) and phaclofen (0.0001 µg/rat) potentiated the impairment effect of MK-801 (0.125 and 0.25 µg/rat) on passive avoidance memory. In conclusion, our results indicated that BLA GABA-B receptors can alter the effect of NMDA inactivation on passive avoidance memory.

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

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 (0.5 µg/rat) and GABAA receptor agonists (muscimol at doses 0.05 and 0.1 µg/rat) or antagonist (bicuculline at doses 0.05 and 0.1 µg/rat) decreased step-through latency during retrieval but did not alter locomotor activity. Results also showed that a subthreshold dose of muscimol (0.025 µg/rat) potentiated impairment induced by (+)-MK-801, whereas bicuculline (0.025 µg/rat) restored it. Furthermore, the highest dose of muscimol (0.5 µg/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.