Participation of the glutamatergic neurotransmission of the inferior colliculus in the modulation of prepulse inhibition of the acoustic startle reflex, motor behavior and social interaction in rats

• Grant number: 12/05021-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2012
• End date: May 31, 2014
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Regina Cláudia Barbosa da Silva
• Grantee: Júlia Flávia Zangrando
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Prepulse inhibition (PPI) is the reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus and is an operational measure of sensorimotor gating. PPI is impaired in schizophrenia patients and can be induced in rats by systemic administration of N-methyl-D-aspartate (NMDA) glutamatergic antagonists such as phencyclidine (PCP), dizocilpine (MK-801) and ketamine. These deficits in PPI can be reversed by antipsychotics drugs. The inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude while large lesions of the IC eliminated the inhibition of acoustic startle. The aim of the present study is to elucidate the role of glutamatergic transmission in the IC, via NMDA receptors, on the expression of acoustic PPI. For that, we will investigate whether unilateral microinjections of MK-801, an NMDA receptor-antagonist (30 nmol/0.5 ¼L) or NMDA (30 nmol/0.5 ¼L) into the IC will affect PPI. In an attempt to establish a parallel with the clinic we will investigate if pre-treatment with antipsychotic drugs, such as haloperidol (0.5 mg/kg), and olanzapine (5.0 mg/kg) will reverse MK-801-induced PPI deficits in rats. Moreover, it will be also evaluated the hyperactivity and social withdrawal in rats, behaviors that correlates well with the positive and negative symptoms of schizophrenia, respectively. (AU)

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)

ZANGRANDO, JULIA; CARVALHEIRA, RENATA; LABBATE, GIOVANNA; MEDEIROS, PRISCILA; LONGO, BEATRIZ MONTEIRO; MELO-THOMAS, LIANA; BARBOSA SILVA, REGINA CLAUDIA. Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats. Behavioural Brain Research, v. 257, p. 77-82, NOV 15 2013. (12/01062-7, 11/01409-4, 12/05021-3, 10/14446-2, 12/06275-9)