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Titolo:
Picrotoxin in the medial prefrontal cortex impairs sensorimotor gating in rats: reversal by haloperidol
Autore:
Japha, K; Koch, M;
Indirizzi:
Univ Tubingen, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 bingen, D-72076 Tubingen, Germany
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 4, volume: 144, anno: 1999,
pagine: 347 - 354
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTRAL TEGMENTAL AREA; DOPAMINE-GLUTAMATE INTERACTIONS; ACOUSTIC STARTLE RESPONSE; GABA(A) RECEPTOR-BINDING; NUCLEUS-ACCUMBENS; PREPULSE INHIBITION; ANIMAL-MODEL; ELECTRICAL-STIMULATION; SCHIZOPHRENIC-PATIENTS; NEURONS;
Keywords:
acoustic startle response; GABA; haloperidol; hippocampus; picrotoxin; prefrontal cortex; prepulse inhibition; schizophrenia; sensorimotor gating;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Koch, M Univ Tubingen, Morgenstelle 28, D-72076 Tubingen, Germany Univ Tubingen Morgenstelle 28 Tubingen Germany D-72076 n, Germany
Citazione:
K. Japha e M. Koch, "Picrotoxin in the medial prefrontal cortex impairs sensorimotor gating in rats: reversal by haloperidol", PSYCHOPHAR, 144(4), 1999, pp. 347-354

Abstract

Rationale: Neuropathological data indicate a GABAergic dysfunction in the prefrontal cortex and hippocampus of schizophrenics. On this basis, the construct validity of an animal model of schizophrenia was tested. Objective: This study assessed prepulse inhibition (PPI) of startle in rats after injections of the GABA antagonist picrotoxin into the prefrontal cortex and theventral hippocampus. It was also tested if reductions in PPI are reversed by the dopamine antagonist haloperidol. PPI is a measure of sensorimotor gating and is impaired in schizophrenia patients. The hypothesis underlying this study was that blockade of prefrontocortical and hippocampal GABA receptors disrupts PPI in a dopamine-dependent way. This hypothesis was based onneuropathological data from schizophrenics indicating a loss of GABAergic neurons in the prefrontal cortex and hippocampus and on the observation that PPI is reduced in schizophrenics. Methods: Picrotoxin (0, 5, 10 ng/0.5 yl) was infused through chronically indwelling cannulae into the medial prefrontal cortex (mPFC), into the lateral prefrontal cortex and into the ventral hippocampus. The effect on PPI was measured directly after picrotoxin infusion. The neuroleptic compound haloperidol (0.1 mg/kg) was administered intraperitoneally 30 min before testing. Results: Picrotoxin in the mPFC dose-dependently reduced PPI and this effect was antagonized by systemic pretreatment with the dopamine antagonist haloperidol. No significant effects on PPI were observed after picrotoxin infusions into the lateral prefrontal cortex or into the ventral hippocampus. Conclusions: These findings indicate that acute blockade of GABA receptors in the mPFC impairs sensorimotor gating in a dopamine-dependent manner. Since PPI in rats has been shown to possess face, predictive, and construct validity as an animal model for some psychotic symptoms, we discuss the potential relevance of our findings for the pathophysiology of schizophrenia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 07:25:33