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Participation of the GABAergic neurotransmission of the inferior colliculus, via activation of 5-HT2A receptors, and its neuroanatomic correlates in the mediation of pre-pulse inhibition response of the acoustic startle reflex and social interaction in ma

Abstract

The relationship between serotonergic dysfunction and schizophrenia began with the discovery of the effects of lysergic acid diethylamide (LSD) which has high affinity for the 5-HT2A receptor. Its activation generates delusions and hallucinations that are positive symptoms of schizophrenia. Another substance, 2,5-dimethoxy-4-iodoamphetamine (DOI), also exhibits hallucinogenic properties being 5-HT2A agonist like LSD. A widely used animal model, based on attentional processes, is the pre-pulse inhibition (PPI) of the acoustic startle reflex. The PPI function is to filter out irrelevant information, enabling the individual to direct their attention to more important aspects of the environment, thus reflecting a pre-attentive process. Patients with schizophrenia exhibit deficits in this response. The primary neuronal pathway mediating PPI response lies in the brainstem, with the inferior colliculus (IC) and the caudal reticular nucleus of the pontine (PnC) being key structures in this circuit. One of the main negative symptoms of schizophrenia is the social withdrawal that leads to important losses in the personal and professional sphere of the individual. A recent study conducted in our laboratory, showed that microinjection of DOI into the IC led to deficits in PPI and social interaction in male Wistar rats. In this context, the present work has as general objective to continue this study, investigating the existence of a functional interaction between serotonergic receptors 5-HT2A in IC and GABAergic inhibitory neurotransmission in this structure. We will verify, through studies of immunohistochemistry, if activation of 5-HT2A receptors by microinjections of DOI into the IC will increase GABAergic neurotransmission in this structure and also in nRCP inhibiting these two structures. We will also investigate whether deficits in IPP responses and social interaction observed after administration of DOI into the IC can be blocked by the concomitant microinjection of bicuculline, a GABAA antagonist, in the nRCP. Additionally, through neurotrace studies, we intend to investigate the existence of a direct inhibitory GABAergic pathway between the IC and the nRCP supposedly involved in the modulation of the IPP response. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE OLIVEIRA, RODOLPHO PEREIRA; DE ANDRADE, JOSE SIMOES; SPINA, MARIANNA; CHAMON, JOAO VITOR; DIAS SILVA, PAULO HENRIQUE; WERDER, ANA KEYLA; ORTOLANI, DANIELA; CARDOSO THOMAZ, LUCAS DE SANTANA; ROMARIZ, SIMONE; RIBEIRO, DANIEL ARAKI; et al. Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress. PLoS One, v. 17, n. 3, p. 19-pg., . (17/17051-8, 14/16634-1)
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; et al. 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. Behavioural Brain Research, v. 448, p. 12-pg., . (17/17051-8, 17/17056-0)

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