5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms.
Summary of "5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms."
Background and Purpose: Serotonin(6) (5-HT(6) ) receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT(6) receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT(6) receptor agonists have been found to enhance and impaired memory. EXPERIMENTAL
This study validates a conditioned emotion response (CER) paradigm in rats and examines the effect of the 5-HT(6) receptor antagonist, SB-271046 (10 mg kg(-1) , i.p.), and agonists, E-6801 (2.5 mg kg(-1) , i.p.) and EMD 386088 (5 mg kg(-1) , i.p.) both given alone and with the muscarinic receptor antagonist, scopolamine (0.3 mg kg(-1) , i.p), and the NMDA receptor antagonist, MK-801 (0.1 mg kg-1, i.p) in CER. KEY
Pairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory, when the rat was returned to the shock chamber 24 h later. Pre-treatment (-20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT(6) receptor antagonist, SB-270146, and agonists, EMD 386088 and E-6801, had little effect on CER freezing when given alone, but all significantly (p≤0.05) reversed scopolamine- and MK-801-induced reduction in freezing. CONCLUSIONS AND
Both 5-HT(6) receptor agonists and antagonist reverse cholinergic- and glutamatergic-induced deficits in associative learning. These findings support the therapeutic potential of 5-HT(6) receptor compounds in the treatment of cognitive dysfunction, such as seen in Alzheimer's disease and schizophrenia. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
School of Biomedical Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
This article was published in the following journal.
Name: British journal of pharmacology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22568655
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02022.x
Medical and Biotech [MESH] Definitions
Serotonin 5-ht1 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.
Serotonin 5-ht2 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.
Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.
Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
Gaba-b Receptor Antagonists
Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.
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