title: Synergistic effect between prelimbic 5-HT3 and CB1 receptors on memory consolidation deficit in adult male Sprague-Dawley rats: An isobologram analysis.
abstract: The serotonergic system has often been defined as a neuromodulator system, and is specifically involved in learning and memory via its various receptors. Serotonin is involved in many of the same processes affected by cannabinoids. The present study investigated the influence of bilateral post-training intra-prelimbic (PL) administrations of serotonergic 5-hydroxytryptamine type-3 (5-HT3) receptor agents on arachidonylcyclopropylamide (ACPA) (cannabinoid CB1 receptor agonist)-induced amnesia, using the step-through inhibitory avoidance (IA) task to assess memory in adult male Sprague-Dawley rats. The results indicated that sole intra-PL microinjection of ACPA (0.1 and 0.5 μg/rat) and 5-HT3 serotonin receptor agonist (m-Chlorophenylbiguanide hydrochloride, m-CPBG; 0.001, 0.01 and 0.1 μg/rat) impaired, whereas Y-25130 (a selective 5-HT3 serotonin receptor antagonist; 0.001 and 0.01 and 0.1 μg/rat) did not alter IA memory consolidation, by itself. Moreover, intra-PL administration of subthreshold dose of m-CPBG (0.0005 μg/rat) potentiated, while Y-25130 (0. 1 μg/rat) restored ACPA-induced memory consolidation deficit. The isobologram analysis showed that there is a synergistic effect between ACPA and m-CPBG on memory consolidation deficit. These findings suggest that 5-HT3 receptor mechanism(s), at least partly, play(s) a role in modulating the effect of ACPA on memory consolidation in the PL area.
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Ahmadi-Mahmoodabadi
authors.affiliation: Institute for Cognitive Science Studies (ICSS), Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: Nasehi@iricss.org.
authors.forename: M
authors.initials: M
authors.lastname: Nasehi
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Emam Ghoreishi
authors.affiliation: Institute for Cognitive Science Studies (ICSS), 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; Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors.forename: M-R
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000633:toxicity; D001362:Avoidance Learning / Q000187:drug effects; D001645:Biguanides / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000633:toxicity; D017366:Serotonin Receptor Agonists / Q000633:toxicity
chemical_list: D001095:Arachidonic Acids; D001645:Biguanides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D063386:Cannabinoid Receptor Agonists; D010078:Oxazines; D043884:Receptor, Cannabinoid, CB1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C119324:arachidonylcyclopropylamide; C070671:azasetron; C065734:1-(3-chlorophenyl)biguanide
keywords: ACPA; Y-25130; inhibitory avoidance (IA) memory; m-CPBG; pre-limbic area