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Additive Effect of Bla Gabaa Receptor Mechanism and (+)-Mk-801 on Memory Retention Deficit, an Isobologram Analysis Publisher Pubmed



Khakpoor M1 ; Nasehi M2 ; Vahdati A1 ; Hoseyni SE1 ; Zarrindast MR2, 3, 4, 5, 6, 7
Authors
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Authors Affiliations
  1. 1. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
  2. 2. Cognitive and Neuroscience Research Center, CNRC, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
  6. 6. Substance Abuse and Dependence Research Center, University of School Welfare and Rehabilitation Sciences, Tehran, Iran
  7. 7. Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

Source: Pharmacology Biochemistry and Behavior Published:2016


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 24 h 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. © 2016 Elsevier Inc. All rights reserved.
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