title: 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.
abstract: Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. 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. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 μL) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 μL) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine.
authors.affiliation: Laboratório de Psicologia Experimental, Departamento de Biociências, Universidade Federal de São Paulo (Unifesp), Av. D. Ana Costa, 95, Santos, SP 11060-001, Brazil.
authors.forename: Julia
authors.initials: J
authors.lastname: Zangrando
authors.forename: Renata
authors.initials: R
authors.lastname: Carvalheira
authors.forename: Giovanna
authors.initials: G
authors.lastname: Labbate
authors.forename: Priscila
authors.initials: P
authors.lastname: Medeiros
authors.forename: Beatriz Monteiro
authors.initials: BM
authors.lastname: Longo
authors.forename: Liana
authors.initials: L
authors.lastname: Melo-Thomas
authors.forename: Regina Claudia Barbosa
authors.initials: RC
authors.lastname: Silva
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007245:Inferior Colliculi / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D000077152:Olanzapine; D011571:Psychoacoustics; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D001569:Benzodiazepines; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000077152:Olanzapine
keywords: Inferior colliculus; MK-801; NMDA; Olanzapine; Prepulse inhibition; Schizophrenia