Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus

Hassen A. Al-Amin, Cynthia Shannon Weickert, Daniel R. Weinberger, Barbara K. Lipska

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Abstract

Background: Abnormalities in the glutamatergic system, glutamate/dopamine/γ-aminobutyric acid interactions, and cortical development are implicated in schizophrenia. Moreover, patients with schizophrenia show symptom exacerbation in response to N-methyl-D-aspartate (NMDA) antagonist drugs. Using an animal model of schizophrenia, we compared the impact of neonatal and adult hippocampal lesions on behavioral responses to MK-801, a noncompetitive NMDA antagonist. Methods: Neonatal rats were lesioned on postnatal day 7. Their motor activity in response to MK-801 was tested at a juvenile age, in adolescence, and in adulthood. We also measured binding of [3H]MK-801 and the expression of NR1 messenger RNA (mRNA) in the medial prefrontal cortex and nucleus accumbens. Adult rats received similar lesions and were tested 4 and 8 weeks after the lesion. Results: As juveniles, neonatally lesioned rats did not differ from control rats in responsiveness to MK-801, whereas in adolescence and adulthood they showed more pronounced hyperactivity than control rats. The adult lesion did not alter behaviors elicited by MK-801. Neonatally lesioned rats showed no apparent changes in [3H]MK-801 binding or expression of the NR1 mRNA. Conclusions: These results suggest that an early lesion of the ventral hippocampus affects development of neural systems involved in MK-801 action without changes at the NMDA receptor level, and they show that the behavioral changes manifest first in early adulthood.

Original languageEnglish
Pages (from-to)528-539
Number of pages12
JournalBiological Psychiatry
Volume49
Issue number6
DOIs
Publication statusPublished - 15 Mar 2001

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Keywords

  • Animal model
  • Behavior
  • Binding
  • Dizocilpine
  • Hippocampus
  • NMDA mRNA
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

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