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Atypical, but Not Typical, Antipsychotic Drugs Reduce Hypersynchronized Prefrontal-Hippocampal Circuits during Psychosis-Like States in Mice: Contribution of 5-HT2A and 5-HT1A Receptors.
Delgado-Sallent, Cristina; Nebot, Pau; Gener, Thomas; Fath, Amanda B; Timplalexi, Melina; Puig, M Victoria.
Afiliación
  • Delgado-Sallent C; Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
  • Nebot P; Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
  • Gener T; Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
  • Fath AB; Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
  • Timplalexi M; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Puig MV; Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
Cereb Cortex ; 32(16): 3472-3487, 2022 08 03.
Article en En | MEDLINE | ID: mdl-34875009
ABSTRACT
Neural synchrony and functional connectivity are disrupted in schizophrenia. We investigated changes in prefrontal-hippocampal neural dynamics during psychosis-like states induced by the NMDAR antagonist phencyclidine and subsequent rescue by two atypical antipsychotic drugs (AAPDs), risperidone and clozapine, and the classical APD haloperidol. The psychotomimetic effects of phencyclidine were associated with prefrontal hypersynchronization, hippocampal desynchronization, and disrupted circuit connectivity. Phencyclidine boosted prefrontal oscillatory power at atypical bands within delta, gamma, and high frequency ranges, while irregular cross-frequency and spike-LFP coupling emerged. In the hippocampus, phencyclidine enhanced delta rhythms but suppressed theta oscillations, theta-gamma coupling, and theta-beta spike-LFP coupling. Baseline interregional theta-gamma coupling, theta phase coherence, and hippocampus-to-cortex theta signals were redirected to delta frequencies. Risperidone and clozapine, but not haloperidol, reduced phencyclidine-induced prefrontal and cortical-hippocampal hypersynchrony. None of the substances restored hippocampal and circuit desynchronization. These results suggest that AAPDs, but not typical APDs, target prefrontal-hippocampal pathways to elicit antipsychotic action. We investigated whether the affinity of AAPDs for serotonin receptors could explain their distinct effects. Serotonin 5-HT2AR antagonism by M100907 and 5-HT1AR agonism by 8-OH-DPAT reduced prefrontal hypersynchronization. Our results point to fundamentally different neural mechanisms underlying the action of atypical versus typical APDs with selective contribution of serotonin receptors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Antipsicóticos / Clozapina / Receptor de Serotonina 5-HT1A / Receptor de Serotonina 5-HT2A Límite: Animals Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2022 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Antipsicóticos / Clozapina / Receptor de Serotonina 5-HT1A / Receptor de Serotonina 5-HT2A Límite: Animals Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2022 Tipo del documento: Article País de afiliación: España