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Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice

RATIONALE: Amylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc),...

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Autores principales: Kalafateli, Aimilia Lydia, Aranäs, Cajsa, Jerlhag, Elisabet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561575/
https://www.ncbi.nlm.nih.gov/pubmed/32651639
http://dx.doi.org/10.1007/s00213-020-05607-8
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author Kalafateli, Aimilia Lydia
Aranäs, Cajsa
Jerlhag, Elisabet
author_facet Kalafateli, Aimilia Lydia
Aranäs, Cajsa
Jerlhag, Elisabet
author_sort Kalafateli, Aimilia Lydia
collection PubMed
description RATIONALE: Amylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc), has attributed them a role as reward regulators. Indeed, acute activation of amylin receptors by the amylin receptor agonist salmon calcitonin (sCT) attenuates alcohol-induced behaviours in rodents. OBJECTIVES: The effects of long-term administration of sCT on alcohol-related behaviours and the molecular mechanisms underlying these processes are not yet elucidated. To fill this knowledge gap, we investigated the effects of sub-chronic sCT treatment on the locomotor stimulatory responses to alcohol in mice and the molecular pathways involved. METHODS: We assessed the behavioural effects of sub-chronic sCT treatment by means of locomotor activity experiments in mice. We used western blot to identify changes of the CTR levels and ex vivo biochemical analysis to detect changes in monoamines and their metabolites. RESULTS: After discontinuation for 5 days of sCT treatment, alcohol did not induce locomotor stimulation in mice pre-treated with sCT when compared with vehicle, without altering secondary behavioural parameters of the locomotor activity experiment or the protein levels of the CTR in reward-related areas in the same set of animals. Moreover, repeated sCT treatment altered monoaminergic neurotransmission in various brain areas, including increased serotonin and decreased dopamine turnover in the VTA. Lastly, we identified a differential effect of repeated sCT and acute alcohol administration on alcohol-induced locomotion in mice, where sCT initially attenuated and later increased this alcohol response. It was further found that this treatment combination did not affect secondary behavioural parameters measured in this locomotor activity experiments. CONCLUSIONS: These data suggest that sub-chronic sCT treatment differentially alters the ability of alcohol to cause locomotor stimulation, possibly through molecular mechanisms involving various neurotransmitter systems and not the CTR levels per se. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00213-020-05607-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-75615752020-10-19 Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice Kalafateli, Aimilia Lydia Aranäs, Cajsa Jerlhag, Elisabet Psychopharmacology (Berl) Original Investigation RATIONALE: Amylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc), has attributed them a role as reward regulators. Indeed, acute activation of amylin receptors by the amylin receptor agonist salmon calcitonin (sCT) attenuates alcohol-induced behaviours in rodents. OBJECTIVES: The effects of long-term administration of sCT on alcohol-related behaviours and the molecular mechanisms underlying these processes are not yet elucidated. To fill this knowledge gap, we investigated the effects of sub-chronic sCT treatment on the locomotor stimulatory responses to alcohol in mice and the molecular pathways involved. METHODS: We assessed the behavioural effects of sub-chronic sCT treatment by means of locomotor activity experiments in mice. We used western blot to identify changes of the CTR levels and ex vivo biochemical analysis to detect changes in monoamines and their metabolites. RESULTS: After discontinuation for 5 days of sCT treatment, alcohol did not induce locomotor stimulation in mice pre-treated with sCT when compared with vehicle, without altering secondary behavioural parameters of the locomotor activity experiment or the protein levels of the CTR in reward-related areas in the same set of animals. Moreover, repeated sCT treatment altered monoaminergic neurotransmission in various brain areas, including increased serotonin and decreased dopamine turnover in the VTA. Lastly, we identified a differential effect of repeated sCT and acute alcohol administration on alcohol-induced locomotion in mice, where sCT initially attenuated and later increased this alcohol response. It was further found that this treatment combination did not affect secondary behavioural parameters measured in this locomotor activity experiments. CONCLUSIONS: These data suggest that sub-chronic sCT treatment differentially alters the ability of alcohol to cause locomotor stimulation, possibly through molecular mechanisms involving various neurotransmitter systems and not the CTR levels per se. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00213-020-05607-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-07-10 2020 /pmc/articles/PMC7561575/ /pubmed/32651639 http://dx.doi.org/10.1007/s00213-020-05607-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Investigation
Kalafateli, Aimilia Lydia
Aranäs, Cajsa
Jerlhag, Elisabet
Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title_full Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title_fullStr Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title_full_unstemmed Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title_short Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
title_sort effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561575/
https://www.ncbi.nlm.nih.gov/pubmed/32651639
http://dx.doi.org/10.1007/s00213-020-05607-8
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