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

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de Oliveira, Rodolpho Pereira ; Yokoyama, Thais ; Thomaz, Lucas de Santana Cardoso ; de Andrade, Jose Simoes ; Santos, Alexia dos Anjos ; Mendonca, Vinicius de Carvalho ; Rosenstock, Tatiana ; Carrera, Marinete Pinheiro ; Medeiros, Priscila ; Cruz, Fabio Cardoso ; Coimbra, Norberto Cysne ; Silva, Regina Claudia Barbosa

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Brain Research; v. 448, p. 12-pg., 2023-04-22.

Resumo

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-HT2A receptors. Activation of these receptors produces perceptual and behavioural changes such as illusions, visual hallucinations and locomotor hyperac-tivity. 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-HT2A 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 microin-jection of the GABAA 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-HT2A receptors may be at least partially involved in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures. (AU)

• Processo FAPESP: 17/17051-8 - Participação da neurotransmissão GABAérgica do colículo inferior, via ativação de receptores 5-HT2A, e seus correlatos neuroanatômicos na mediação das respostas de inibição por pré- pulso do reflexo de sobressalto acústico e interação social em ratos Wist
• Beneficiário: Regina Cláudia Barbosa da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/17056-0 - Participação da neurotransmissão GABAérgica do colículo inferior, via ativação de receptores 5-HT2A, na mediação das respostas de inibição por pré- pulso do reflexo de sobressalto acústico e interação social em ratos Wistar machos
• Beneficiário: Rodolpho Pereira de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado