Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus

Hassen Al Amin, D. R. Weinberger, B. K. Lipska

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Neonatal lesions of the ventral hippocampus in rats produce changes in spontaneous and pharmacologically induced dopamine-dependent behaviors that emerge in early adulthood. Neural mechanisms underlying these changes may have implications for understanding the neurobiology of schizophrenia, putatively a neurodevelopmental disorder. In this study, we evaluated the effects of MK-801 (dizocilpine), on automated measures of distance traveled and stereotypies in adult rats with neonatal (postnatal day 7) lesions, and tested the effects of haloperidol, clozapine and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) antagonist LY293558 on the MK-801-induced behaviors. The lesioned rats showed significantly greater increases in motor activity after 0.05 and 0.1 mg/kg of MK-801 than did controls. Both haloperidol (0.1 and 0.4 mg/kg) and clozapine (4 and 10 mg/kg) reduced hyperlocomotion elicited by 0.2 mg/kg MK-801 in the ventral hippocampus (VH)-lesioned and sham rats. Haloperidol was more potent than clozapine in decreasing MK-801-induced stereotypy, especially in the lesioned rats. Moreover, an AMPA antagonist normalized exaggerated MK-801-induced hyperolocomotion in the lesioned rats at doses that had no effect in controls. These results demonstrate that the lesioned rats are more sensitive to MK-801 during adulthood than control rats, and that antidopaminergic drugs as well as AMPA antagonists antagonize the MK-801-induced behaviors. The neonatal lesion rat model may be useful to further our understanding of the interactions between dopamine and glutamate and their role in the pathophysiology of schizophrenia. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalBehavioural Pharmacology
Volume11
Issue number3-4
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Hyperkinesis
Dizocilpine Maleate
Hippocampus
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Clozapine
Haloperidol
tezampanel
Dopamine
Schizophrenia
Neurobiology
Glutamic Acid
Motor Activity

Keywords

  • AMPA antagonist
  • Animal model
  • Behavior
  • Dizocilpine
  • Hippocampus
  • LY293558
  • Neuroleptics
  • Rat
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus. / Al Amin, Hassen; Weinberger, D. R.; Lipska, B. K.

In: Behavioural Pharmacology, Vol. 11, No. 3-4, 2000, p. 269-278.

Research output: Contribution to journalArticle

@article{602c8e1750d54634b9175ebf67280071,
title = "Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus",
abstract = "Neonatal lesions of the ventral hippocampus in rats produce changes in spontaneous and pharmacologically induced dopamine-dependent behaviors that emerge in early adulthood. Neural mechanisms underlying these changes may have implications for understanding the neurobiology of schizophrenia, putatively a neurodevelopmental disorder. In this study, we evaluated the effects of MK-801 (dizocilpine), on automated measures of distance traveled and stereotypies in adult rats with neonatal (postnatal day 7) lesions, and tested the effects of haloperidol, clozapine and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) antagonist LY293558 on the MK-801-induced behaviors. The lesioned rats showed significantly greater increases in motor activity after 0.05 and 0.1 mg/kg of MK-801 than did controls. Both haloperidol (0.1 and 0.4 mg/kg) and clozapine (4 and 10 mg/kg) reduced hyperlocomotion elicited by 0.2 mg/kg MK-801 in the ventral hippocampus (VH)-lesioned and sham rats. Haloperidol was more potent than clozapine in decreasing MK-801-induced stereotypy, especially in the lesioned rats. Moreover, an AMPA antagonist normalized exaggerated MK-801-induced hyperolocomotion in the lesioned rats at doses that had no effect in controls. These results demonstrate that the lesioned rats are more sensitive to MK-801 during adulthood than control rats, and that antidopaminergic drugs as well as AMPA antagonists antagonize the MK-801-induced behaviors. The neonatal lesion rat model may be useful to further our understanding of the interactions between dopamine and glutamate and their role in the pathophysiology of schizophrenia. (C) 2000 Lippincott Williams and Wilkins.",
keywords = "AMPA antagonist, Animal model, Behavior, Dizocilpine, Hippocampus, LY293558, Neuroleptics, Rat, Schizophrenia",
author = "{Al Amin}, Hassen and Weinberger, {D. R.} and Lipska, {B. K.}",
year = "2000",
language = "English",
volume = "11",
pages = "269--278",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams and Wilkins",
number = "3-4",

}

TY - JOUR

T1 - Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus

AU - Al Amin, Hassen

AU - Weinberger, D. R.

AU - Lipska, B. K.

PY - 2000

Y1 - 2000

N2 - Neonatal lesions of the ventral hippocampus in rats produce changes in spontaneous and pharmacologically induced dopamine-dependent behaviors that emerge in early adulthood. Neural mechanisms underlying these changes may have implications for understanding the neurobiology of schizophrenia, putatively a neurodevelopmental disorder. In this study, we evaluated the effects of MK-801 (dizocilpine), on automated measures of distance traveled and stereotypies in adult rats with neonatal (postnatal day 7) lesions, and tested the effects of haloperidol, clozapine and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) antagonist LY293558 on the MK-801-induced behaviors. The lesioned rats showed significantly greater increases in motor activity after 0.05 and 0.1 mg/kg of MK-801 than did controls. Both haloperidol (0.1 and 0.4 mg/kg) and clozapine (4 and 10 mg/kg) reduced hyperlocomotion elicited by 0.2 mg/kg MK-801 in the ventral hippocampus (VH)-lesioned and sham rats. Haloperidol was more potent than clozapine in decreasing MK-801-induced stereotypy, especially in the lesioned rats. Moreover, an AMPA antagonist normalized exaggerated MK-801-induced hyperolocomotion in the lesioned rats at doses that had no effect in controls. These results demonstrate that the lesioned rats are more sensitive to MK-801 during adulthood than control rats, and that antidopaminergic drugs as well as AMPA antagonists antagonize the MK-801-induced behaviors. The neonatal lesion rat model may be useful to further our understanding of the interactions between dopamine and glutamate and their role in the pathophysiology of schizophrenia. (C) 2000 Lippincott Williams and Wilkins.

AB - Neonatal lesions of the ventral hippocampus in rats produce changes in spontaneous and pharmacologically induced dopamine-dependent behaviors that emerge in early adulthood. Neural mechanisms underlying these changes may have implications for understanding the neurobiology of schizophrenia, putatively a neurodevelopmental disorder. In this study, we evaluated the effects of MK-801 (dizocilpine), on automated measures of distance traveled and stereotypies in adult rats with neonatal (postnatal day 7) lesions, and tested the effects of haloperidol, clozapine and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) antagonist LY293558 on the MK-801-induced behaviors. The lesioned rats showed significantly greater increases in motor activity after 0.05 and 0.1 mg/kg of MK-801 than did controls. Both haloperidol (0.1 and 0.4 mg/kg) and clozapine (4 and 10 mg/kg) reduced hyperlocomotion elicited by 0.2 mg/kg MK-801 in the ventral hippocampus (VH)-lesioned and sham rats. Haloperidol was more potent than clozapine in decreasing MK-801-induced stereotypy, especially in the lesioned rats. Moreover, an AMPA antagonist normalized exaggerated MK-801-induced hyperolocomotion in the lesioned rats at doses that had no effect in controls. These results demonstrate that the lesioned rats are more sensitive to MK-801 during adulthood than control rats, and that antidopaminergic drugs as well as AMPA antagonists antagonize the MK-801-induced behaviors. The neonatal lesion rat model may be useful to further our understanding of the interactions between dopamine and glutamate and their role in the pathophysiology of schizophrenia. (C) 2000 Lippincott Williams and Wilkins.

KW - AMPA antagonist

KW - Animal model

KW - Behavior

KW - Dizocilpine

KW - Hippocampus

KW - LY293558

KW - Neuroleptics

KW - Rat

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0033947809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033947809&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 269

EP - 278

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

IS - 3-4

ER -