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
APPROACH:
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
RESULTS:
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
IMPLICATIONS:
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.
Affiliation
School of Biomedical Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
Journal Details
This article was published in the following journal.
Name: British journal of pharmacology
ISSN: 1476-5381
Pages:
Links
- 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.
Drug Antagonism
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.
Memory
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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