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Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission.
Neuropharmacology. 2008 Jun; 54(7):1041-50.N

Abstract

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-HT(1B) receptors are located as autoreceptors on 5-HT axons and heteroreceptors on non-serotonergic terminals. This study examined the role of the 5-HT(1B) receptor in one-trial aversive contextual learning using the passive avoidance (PA) task in NMRI mice. Subcutaneous administration of the 5-HT(1B) receptor agonist anpirtoline (0.1-1.0mg/kg) before PA training impaired retention performance 24h later. Combined administration of anpirtoline with the selective 5-HT(1B) receptor antagonist NAS-181 (0.1-1.0mg/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 (0.1mg/kg), when administered prior to, but not after, scopolamine. In addition, NAS-181 attenuated PA impairments induced by MK-801 (0.3mg/kg). These findings indicate that 5-HT(1B) 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-HT(1B) 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-HT(1B) heteroreceptors may represent a novel therapeutic strategy for restoration of deficient cholinergic and glutamatergic neurotransmission contributing to memory disorders.

Authors+Show Affiliations

Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18394658

Citation

Eriksson, Therese M., et al. "Blockade of 5-HT 1B Receptors Facilitates Contextual Aversive Learning in Mice By Disinhibition of Cholinergic and Glutamatergic Neurotransmission." Neuropharmacology, vol. 54, no. 7, 2008, pp. 1041-50.
Eriksson TM, Madjid N, Elvander-Tottie E, et al. Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission. Neuropharmacology. 2008;54(7):1041-50.
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, 54(7), 1041-50. https://doi.org/10.1016/j.neuropharm.2008.02.007
Eriksson TM, et al. Blockade of 5-HT 1B Receptors Facilitates Contextual Aversive Learning in Mice By Disinhibition of Cholinergic and Glutamatergic Neurotransmission. Neuropharmacology. 2008;54(7):1041-50. PubMed PMID: 18394658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission. AU - Eriksson,Therese M, AU - Madjid,Nather, AU - Elvander-Tottie,Elin, AU - Stiedl,Oliver, AU - Svenningsson,Per, AU - Ogren,Sven Ove, Y1 - 2008/04/03/ PY - 2007/09/05/received PY - 2007/12/21/revised PY - 2008/02/11/accepted PY - 2008/4/9/pubmed PY - 2008/10/15/medline PY - 2008/4/9/entrez SP - 1041 EP - 50 JF - Neuropharmacology JO - Neuropharmacology VL - 54 IS - 7 N2 - 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-HT(1B) receptors are located as autoreceptors on 5-HT axons and heteroreceptors on non-serotonergic terminals. This study examined the role of the 5-HT(1B) receptor in one-trial aversive contextual learning using the passive avoidance (PA) task in NMRI mice. Subcutaneous administration of the 5-HT(1B) receptor agonist anpirtoline (0.1-1.0mg/kg) before PA training impaired retention performance 24h later. Combined administration of anpirtoline with the selective 5-HT(1B) receptor antagonist NAS-181 (0.1-1.0mg/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 (0.1mg/kg), when administered prior to, but not after, scopolamine. In addition, NAS-181 attenuated PA impairments induced by MK-801 (0.3mg/kg). These findings indicate that 5-HT(1B) 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-HT(1B) 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-HT(1B) heteroreceptors may represent a novel therapeutic strategy for restoration of deficient cholinergic and glutamatergic neurotransmission contributing to memory disorders. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/18394658/Blockade_of_5_HT_1B_receptors_facilitates_contextual_aversive_learning_in_mice_by_disinhibition_of_cholinergic_and_glutamatergic_neurotransmission_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00048-8 DB - PRIME DP - Unbound Medicine ER -