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1. The bidirectional effect of prelimbic 5-hydroxytryptamine type-4 (5-HT4) receptors on ACPA-mediated aversive memory impairment in adult male Sprague-Dawley rats

Author

Nargol Ahmadi-Mahmoodabadi, Masoumeh Emamghoreishi, Mohammad Nasehi, and Mohammad-Reza Zarrindast

Subjects
acpa, pre-limbic cortex, passive avoidance memory, rs23597-190, rs67333, Medicine
Abstract

Objective(s): This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. Materials and Methods: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 μl/rat into the PL area (0.3 μl per side).Results: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 μg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 μg/rat with ineffective (0.001 μg/rat) or effective (0.1 μg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 μg/rat); but its concomitant use with an effective dose of ACPA (0.1 μg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity.Conclusion: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors.

Published
2021
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2. Synergistic effect between prelimbic 5-HT3 and CB1 receptors on memory consolidation deficit in adult male Sprague-Dawley rats: An isobologram analysis

Author

Mohammad-Reza Zarrindast, M. Emam Ghoreishi, Mohammad Nasehi, and Nargol Ahmadi-Mahmoodabadi

Subjects
0301 basic medicine, Agonist, Male, medicine.drug_class, medicine.medical_treatment, Biguanides, Arachidonic Acids, Pharmacology, Motor Activity, Serotonergic, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Oxazines, medicine, Avoidance Learning, Reaction Time, Serotonin receptor antagonist, Animals, Arachidonylcyclopropylamide, Serotonin receptor agonist, Cannabinoid Receptor Agonists, Cerebral Cortex, Memory Disorders, Dose-Response Relationship, Drug, Chemistry, General Neuroscience, Drug Synergism, Bridged Bicyclo Compounds, Heterocyclic, Rats, Serotonin Receptor Agonists, Disease Models, Animal, 030104 developmental biology, Memory consolidation, Serotonin, Cannabinoid, Serotonin Antagonists, Receptors, Serotonin, 5-HT3, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
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.

Published
2015

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