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

Mitra Khakpoor; Salar Vaseghi; Mohammad-Hossein Mohammadi-Mahdiabadi-Hasani; Mohammad Nasehi

doi:10.1016/j.bbr.2021.113313

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

Behav Brain Res. 2021 Jul 9:409:113313. doi: 10.1016/j.bbr.2021.113313. Epub 2021 Apr 20.

Authors

Mitra Khakpoor¹, Salar Vaseghi², Mohammad-Hossein Mohammadi-Mahdiabadi-Hasani³, Mohammad Nasehi⁴

Affiliations

¹ Department of Basic Science, Farhangian University, Tehran, Iran; Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
² Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
³ Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address: Nasehi@iricss.org.

PMID: 33891976
DOI: 10.1016/j.bbr.2021.113313

Abstract

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.

Keywords: Baclofen; Basolateral amygdala; MK-801; Passive avoidance memory; Phaclofen.

MeSH terms

Animals
Avoidance Learning / drug effects*
Baclofen / analogs & derivatives
Baclofen / pharmacology
Basolateral Nuclear Complex / drug effects*
Behavior, Animal / drug effects*
Disease Models, Animal
Dizocilpine Maleate / pharmacology
Excitatory Amino Acid Antagonists / administration & dosage
Excitatory Amino Acid Antagonists / pharmacology*
GABA-B Receptor Agonists / administration & dosage
GABA-B Receptor Agonists / pharmacology*
GABA-B Receptor Antagonists / administration & dosage
GABA-B Receptor Antagonists / pharmacology*
Male
Memory Disorders / chemically induced*
Memory Disorders / drug therapy*
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

Excitatory Amino Acid Antagonists
GABA-B Receptor Agonists
GABA-B Receptor Antagonists
Receptors, N-Methyl-D-Aspartate
phaclofen
Dizocilpine Maleate
Baclofen