Hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus and the effects of pretreatment with haloperidol and clozapine.
Neuroscience
; 103(2): 325-35, 2001.
Article
en En
| MEDLINE
| ID: mdl-11246148
ABSTRACT
This study re-examined the hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the rat ventral hippocampus and compared how both effects were affected by pretreatment with either haloperidol or clozapine. While the hyperactivity is thought to depend on dopamine receptor activation in the nucleus accumbens, the dopamine D2-class receptor blocker haloperidol failed to antagonize the disruption of prepulse inhibition in previous studies. However, an ameliorative effect of the atypical neuroleptic clozapine on disruption of prepulse inhibition was suggested by our previous experiments [Zhang et al. (1999) NeuroReport 10, 1-6]. In the present study, bilateral infusion of N-methyl-D-aspartate (0.5microg/side) into the ventral hippocampus of Wistar rats increased open field locomotor activity and disrupted prepulse inhibition. Both effects were observed immediately after infusion but disappeared 24h later. Injection of haloperidol (0.2mg/kg) or clozapine (5mg/kg), 45min prior to N-methyl-D-aspartate infusion, totally antagonized the hyperactivity but did not affect the disruption of prepulse inhibition. We conclude that dopaminergic mechanisms are differentially involved in the hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus. Activation of accumbal dopamine receptors, which is blocked by clozapine and haloperidol to a comparable extent, seems to be crucial for the hyperactivity but not the disruption of prepulse inhibition. The present finding that both clozapine and haloperidol failed to antagonize the disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus is discussed with respect to our previous contrary finding concerning the ameliorative effect of clozapine and with respect to the disruption of prepulse inhibition in rats being considered as a model of sensorimotor gating deficits in schizophrenia.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antagonistas de la Serotonina
/
Clozapina
/
Receptores de N-Metil-D-Aspartato
/
Antagonistas de Dopamina
/
Haloperidol
/
Hipercinesia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2001
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA