Prepulse inhibition of the acoustic startle reflex impairment by 5-HT2A receptor activation in the inferior colliculus is prevented by GABAA receptor blockade in the pedunculopontine tegmental nucleus.

Autor: de Oliveira RP; Laboratory of Psychobiology of Schizophrenia, Departmentof Biosciences, Federal University of São Paulo (UNIFESP), Silva Jardim Street 136, Santos, 11015-020 São Paulo, Brazil., Yokoyama T; Department of Pharmacology, - Federal University of São Paulo (UNIFESP), São Paulo, SP 04023-062, Brazil., Cardoso Thomaz LS; Laboratory of Psychobiology of Schizophrenia, Departmentof Biosciences, Federal University of São Paulo (UNIFESP), Silva Jardim Street 136, Santos, 11015-020 São Paulo, Brazil., de Andrade JS; Laboratory of Psychobiology of Schizophrenia, Departmentof Biosciences, Federal University of São Paulo (UNIFESP), Silva Jardim Street 136, Santos, 11015-020 São Paulo, Brazil., Santos ADA; Department of Pharmacology, - Federal University of São Paulo (UNIFESP), São Paulo, SP 04023-062, Brazil., de Carvalho Mendonça V; Laboratory of Psychobiology of Schizophrenia, Departmentof Biosciences, Federal University of São Paulo (UNIFESP), Silva Jardim Street 136, Santos, 11015-020 São Paulo, Brazil., Rosenstock T; Sygnature Discovery, Department of Bioscience, BioCity, Pennyfoot Street, Nottingham NG1 1GR, United Kingdom., Pinheiro Carrera M; Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602 RJ, Brazil., Medeiros P; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, RibeirãoPreto Medical School of the Univertsity of São Paulo (FMRP-USP), Av. Bandeirantes, 30900, RibeirãoPreto, 14049-900 São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotion, Department of Surgery and Anatomy, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil; Institute of Neuroscience and Behavior (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220 São Paulo, Brazil; Interdisciplinary Center for PainCare, Federal Universityof São Carlos (UFSCar), Universidade Federal de São Carlos, Rodovia Washington Luiz, Km 235, Caixa Postal 676, CEP 13565-905 SP, Brazil; Department of General and Specialized Nursing - EERP/USP RibeirãoPreto College of Nursing - USP, Brazil., Cruz FC; Department of Pharmacology, - Federal University of São Paulo (UNIFESP), São Paulo, SP 04023-062, Brazil., Coimbra NC; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, RibeirãoPreto Medical School of the Univertsity of São Paulo (FMRP-USP), Av. Bandeirantes, 30900, RibeirãoPreto, 14049-900 São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotion, Department of Surgery and Anatomy, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 São Paulo, Brazil; Institute of Neuroscience and Behavior (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220 São Paulo, Brazil., Silva RCB; Laboratory of Psychobiology of Schizophrenia, Departmentof Biosciences, Federal University of São Paulo (UNIFESP), Silva Jardim Street 136, Santos, 11015-020 São Paulo, Brazil; Institute of Neuroscience and Behavior (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220 São Paulo, Brazil. Electronic address: rcb.silva@unifesp.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2023 Jun 25; Vol. 448, pp. 114436. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1016/j.bbr.2023.114436
Abstrakt: The relationship between serotonin dysfunction and schizophrenia commenced with the discovery of the effects of lysergic acid diethylamide (LSD) that has high affinity for 5-HT 2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperactivity. Using prepulse inhibition (PPI) of the acoustic startle, which is impaired in schizophrenia,we aimed to investigate:i) the existence of a direct and potentially inhibitory neural pathway between the inferior colliculus (IC) and the pedunculopontine tegmental nucleus (PPTg) involved in the mediation of PPI responses by a neural tract tracing procedure;ii) if the microinjection of the 5-HT 2A receptors agonist DOI in IC would activate neurons in this structure and in the PPTg by a c-Fos protein immunohistochemistry study;iii) whether the deficits in PPI responses, observed after the administration of DOI in the IC, could be prevented by the concomitant microinjection of the GABA A receptor antagonist bicuculline in the PPTg.Male Wistar rats were used in this study. An IC-PPTg reciprocated neuronal pathway was identified by neurotracing. The number of c-Fos labelled cells was lower in the DOI group in IC and PPTg, suggesting that this decrease could be due to the high levels of GABA in both structures. The concomitant microinjections of bicuculline in PPTg and DOI in IC prevented the PPI deficit observed after the IC microinjection of DOI. Our findings suggest that IC 5-HT 2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures.
Competing Interests: Declaration of Competing Interest All authors have seen and agree with the contents of the manuscript and there is no financial interest or personal relationships with other people or organizations that could inappropriately influence their work. There is not a conflict of interest with respect to the work presented herein.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: