Involvement of CA1 GABAA Receptors in Ketamine-Induced Impairment of Spatial and Non-Spatial Novelty Detection in Mice


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Abstract

Inhibitory GABAergic and excitatory glutamatergic neurons from multiple brain areas, send fibers to the hippocampal CA1 region. NMDA receptors have been identified as important compoents of the brain system underlying memory formation, which that through an increase in glutamate-mediated neurotransmission. Ketamine and other NMDA receptor antagonists produce deficits in cognitive tasks, including both spatial and non-spatial memory. In the current study, we tested whether the activation or inhibition of GABAA receptors in CA1 hippocampal of mice has an impact on ketamine (NMDA antagonist) induced spatial and non-spatial novelty detection deficits. Adult male mice weighing between 25–30 g were used. The open-field method was used to evaluate spatial and non-spatial memory information. Data obtained from the present study revealed that an intra-CA1 injection with a sub-threshold dose the GABAA receptor antagonist bicuculline (0.0625 µg mouse) disrupted spatial memory but restored non-spatial memory induced by lower and higher doses of ketamine (0.05 and 0.01 mg/kg) respectively. Meanwhile, the co-administration of the intra-CA1 injection with a sub-threshold dose of muscimol (GABAA receptor agonist at 0.25 µg/mouse) and a lower dose of ketamine could only impair the ability of non-spatial change detection but could not alter spatial novelty. In conclusion, ketamine (which contributes to the impairment of memory trace stored in the hippocampus) may be generated from GABAA receptors of CA1 neurons and their blockade could prevent these effects.

About the authors

Arash Khanegheini

Institute for Cognitive Science Studies (ICSS)

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Tehran

Gholam Hossein Meftahi

Neuroscience Research Center

Author for correspondence.
Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Niavaran, Araj st., Tehran

Mohammad Reza Zarrindast

Institute for Cognitive Science Studies (ICSS)

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Tehran

Mohammad Reza Afarinesh

Kerman Neuroscience Research Center, Institute of Neuropharmachology

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Kerman

Hedayat Sahraei

Neuroscience Research Center

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Niavaran, Araj st., Tehran

Gila Pirzad Jahromi

Neuroscience Research Center

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Niavaran, Araj st., Tehran

Shima Shahyad

Neuroscience Research Center

Email: hossein.meftahi@bmsu.ac.ir
Iran, Islamic Republic of, Niavaran, Araj st., Tehran

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