Mohammad Nasehi1, Niyousha Alaghmandan-Motlagh2, Mohaddeseh Ebrahimi-Ghiri3, Mohammad Nami4,5, Mohammad-Reza Zarrindast6,7,8,9,10. 1. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Nasehi@iricss.org. 2. Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Northern Branch, Tehran, Iran. 3. Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran. 4. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. 5. Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir. 7. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir. 8. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran. zarinmr@ams.ac.ir. 9. Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. zarinmr@ams.ac.ir. 10. Institute for Cognitive Science Studies (ICSS), Tehran, Iran. zarinmr@ams.ac.ir.
Abstract
RATIONALE: Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. METHODS: Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. RESULTS: Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. CONCLUSIONS: Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.
RATIONALE: Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. METHODS: Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. RESULTS: Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. CONCLUSIONS: Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoidCB1 signaling upon spatial change and novelty discrimination memory functions.
Authors: István Katona; Gabriella M Urbán; Matthew Wallace; Catherine Ledent; Kwang-Mook Jung; Daniele Piomelli; Ken Mackie; Tamás F Freund Journal: J Neurosci Date: 2006-05-24 Impact factor: 6.167