Abstract
Background
Neonatal ventral hippocampal (NVH) lesions in rats induce behavioral abnormalities
at adulthood thought to simulate some aspects of the positive, negative, and cognitive
deficits classically observed in schizophrenic patients. Such lesions induce a postpubertal
emergence of prepulse inhibition (PPI) deficits of the startle reflex reminiscent
of the sensorimotor gating deficits observed in a majority of schizophrenic patients.
To study the potential involvement of the glycinergic neurotransmission in such deficits,
we investigated the capacity of glycine (an obligatory N-methyl-d-aspartate [NMDA] receptor co-agonist) and ORG 24598 (a selective glycine transporter
1 inhibitor) to reverse NVH lesion–induced PPI deficits in rats.
Methods
Ibotenic acid was injected bilaterally into the ventral hippocampus of 7-day-old pups.
Prepulse inhibition of the startle reflex was measured at adulthood.
Results
Glycine (.8 and 1.6 g/kg IP) and ORG 24598 (10 mg/kg IP) fully and partially reversed
lesion-induced PPI deficits, respectively.
Conclusions
These findings confirm that an impaired glutamatergic neurotransmission may be responsible
for PPI deficits exhibited by NVH-lesioned rats and support the hypoglutamatergic
hypothesis of schizophrenia. They also suggest that drugs acting either directly at
the NMDA receptor glycine site or indirectly on the glycine transporter 1 could offer
promising targets for the development of novel therapies for schizophrenia.
Keywords
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Article info
Publication history
Accepted:
March 23,
2003
Received in revised form:
March 14,
2003
Received:
December 2,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
