Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission
| Autor: | Nather Madjid, Sven Ove Ögren, Per Svenningsson, E. Elvander-Tottie, Oliver Stiedl, Therese Eriksson |
|---|---|
| Přispěvatelé: | Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam 2008, Functional Genomics |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Agonist
Male medicine.drug_class Pyridines Morpholines Scopolamine Glutamic Acid Neurotransmission Synaptic Transmission Cholinergic Antagonists Cellular and Molecular Neuroscience Glutamatergic Mice Piperidines SDG 3 - Good Health and Well-being medicine Avoidance Learning Reaction Time Animals Benzopyrans 5-HT receptor Pharmacology Analysis of Variance Behavior Animal Dose-Response Relationship Drug Muscarinic antagonist Receptor antagonist Acetylcholine Serotonin Receptor Agonists Receptor Serotonin 5-HT1B NMDA receptor Cholinergic Serotonin Antagonists Dizocilpine Maleate Psychology Neuroscience Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Eriksson, T M, Madjid, N, Elvander-Tottie, E, Stiedl, O, Svenningsson, P & Ogren, S O 2008, ' Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission ', Neuropharmacology, vol. 54, pp. 1041-1050 . https://doi.org/10.1016/j.neuropharm.2008.02.007 Neuropharmacology, 54, 1041-1050. Elsevier Limited |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2008.02.007 |
| Popis: | Serotonergic (5-HT) neurotransmission plays a role in learning and memory processes, but the physiological role of various receptor subtypes is not well characterised. Among these, 5-HT1B receptors are located as autoreceptors on 5-HT axons and heteroreceptors on non-serotonergic terminals. This study examined the role of the 5-HT1B receptor in one-trial aversive contextual learning using the passive avoidance (PA) task in NMRI mice. Subcutaneous administration of the 5-HT1B receptor agonist anpirtoline (0.1–1.0 mg/kg) before PA training impaired retention performance 24 h later. Combined administration of anpirtoline with the selective 5-HT1B receptor antagonist NAS-181 (0.1–1.0 mg/kg) fully blocked the impairments. Administration of NAS-181 alone dose-dependently improved PA retention performance. This facilitatory effect was blocked by subthreshold doses of both the muscarinic antagonist scopolamine (0.03 mg/kg) and the NMDA receptor antagonist MK-801 (0.03 mg/kg). NAS-181 also fully blocked the PA impairments induced by an amnesic dose of scopolamine (0.1 mg/kg), when administered prior to, but not after, scopolamine. In addition, NAS-181 attenuated PA impairments induced by MK-801 (0.3 mg/kg). These findings indicate that 5-HT1B receptors are activated at basal levels of 5-HT transmission. The facilitatory effect of NAS-181 involved alleviation of an inhibitory 5-HT tone mediated via 5-HT1B receptors on cholinergic and glutamatergic transmission. This disinhibition is expected to occur in neuronal circuits involved in contextual learning including the hippocampus and interconnected cortico-limbic regions. Blockade of brain 5-HT1B heteroreceptors may represent a novel therapeutic strategy for restoration of deficient cholinergic and glutamatergic neurotransmission contributing to memory disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect