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Serotonin 5-HT 1A, 5-HT 2A and dopamine D 2 receptors strongly influence prefronto-hippocampal neural networks in alert mice: contribution to the actions of risperidone

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dc.contributor.author Gener, Thomas
dc.contributor.author Tauste Campo, Adrià, 1982-
dc.contributor.author Alemany González, Maria, 1991-
dc.contributor.author Nebot Forcada, Pau
dc.contributor.author Delgado-Sallent, Cristina
dc.contributor.author Chanovas Colomé, Jordi
dc.contributor.author Puig Velasco, María Victoria
dc.date.accessioned 2020-03-09T08:26:53Z
dc.date.issued 2019
dc.identifier.citation Gener T, Tauste Campo A, Alemany-González M, Nebot P, Delgado-Sallent C, Chanovas J. et al. Serotonin 5-HT1A, 5-HT2A and dopamine D2 receptors strongly influence prefronto-hippocampal neural networks in alert mice: Contribution to the actions of risperidone. Neuropharmacology. 2019 Nov 1; 158: 107743. DOI: 10.1016/j.neuropharm.2019.107743
dc.identifier.issn 0028-3908
dc.identifier.uri http://hdl.handle.net/10230/43836
dc.description.abstract Atypical antipsychotic drugs (APDs) used to treat positive and negative symptoms in schizophrenia block serotonin receptors 5-HT2AR and dopamine receptors D2R and stimulate 5-HT1AR directly or indirectly. However, the exact cellular mechanisms mediating their therapeutic actions remain unresolved. We recorded neural activity in the prefrontal cortex (PFC) and hippocampus (HPC) of freely-moving mice before and after acute administration of 5-HT1AR, 5-HT2AR and D2R selective agonists and antagonists and atypical APD risperidone. We then investigated the contribution of the three receptors to the actions of risperidone on brain activity via statistical modeling and pharmacological reversal (risperidone + 5-HT1AR antagonist WAY-100635, risperidone + 5-HT2A/2CR agonist DOI, risperidone + D2R agonist quinpirole). Risperidone, 5-HT1AR agonism with 8-OH-DPAT, 5-HT2AR antagonism with M100907, and D2R antagonism with haloperidol reduced locomotor activity of mice that correlated with a suppression of neural spiking, power of theta and gamma oscillations in PFC and HPC, and reduction of PFC-HPC theta phase synchronization. By contrast, activation of 5-HT2AR with DOI enhanced high-gamma oscillations in PFC and PFC-HPC high gamma functional connectivity, likely related to its hallucinogenic effects. Together, power changes, regression modeling and pharmacological reversals suggest an important role of 5-HT1AR agonism and 5-HT2AR antagonism in risperidone-induced alterations of delta, beta and gamma oscillations, while D2R antagonism may contribute to risperidone-mediated changes in delta oscillations. This study provides novel insight into the neural mechanisms for widely prescribed psychiatric medication targeting the serotonin and dopamine systems in two regions involved in the pathophysiology of schizophrenia.
dc.description.sponsorship This work was supported by the Brain and Behavior Research Foundation (NARSAD Young Investigator Award 23014), SAF2013-49129-C2-2-R and SAF2016-80726-R (AEI / FEDER, UE) by the Spanish Ministry of Economy and Competitiveness (MINECO; to MVP). M.V. Puig is a Ramon y Cajal Investigator (RyC-2012-10042), M. Alemany a FPI predoctoral fellow (BES-2014-070429) from MINECO, and C. Delgado a FI predoctoral fellow (2018FI_B_00112)from the Generalitat de Catalunya (AGAUR)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Neuropharmacology. 2019 Nov 1;158:107743
dc.rights © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2019.107743
dc.title Serotonin 5-HT 1A, 5-HT 2A and dopamine D 2 receptors strongly influence prefronto-hippocampal neural networks in alert mice: contribution to the actions of risperidone
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.neuropharm.2019.107743
dc.subject.keyword Antipsychotic drug
dc.subject.keyword Hippocampus
dc.subject.keyword In vivo electrophysiology
dc.subject.keyword Neural synchronization
dc.subject.keyword Prefrontal cortex
dc.subject.keyword Schizophrenia
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-49129-C2-2-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80726-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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