title: 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 (0.5 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.
authors: Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
authors: Mitra
authors: M
authors: Khakpoor
authors: Cognitive and Neuroscience Research Center, CNRC, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: Nasehi@iricss.org.
authors: Mohammad
authors: M
authors: Nasehi
authors: Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
authors: Akbar
authors: A
authors: Vahdati
authors: Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
authors: Seyed-Ebrahim
authors: SE
authors: Hoseyni
authors: Cognitive and Neuroscience Research Center, CNRC, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran; Substance Abuse and Dependence Research Center, University of School Welfare and Rehabilitation Sciences, Tehran, Iran; Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors: Mohammad-Reza
authors: MR
authors: Zarrindast
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D016291:Dizocilpine Maleate
keywords: (+)-MK-801; BLA; Bicuculline; Muscimol; Step-through