Lesion size and amphetamine hyperlocomotion after neonatal ventral hippocampal lesions: more is less.

ABSTRACT

Neonatal hippocampal lesions in rats produce behavioral and neurochemical abnormalities post-puberty that are used in animal models for developmentally linked pathology in schizophrenia. In one model, adult rats exhibit enhanced sensitivity to the locomotor-activating effects of amphetamine, if they had sustained excitotoxic lesions of the ventral hippocampus on post-natal day 7. The hippocampal elements responsible for these lesion-induced developmental changes have not been fully characterized. The present study assessed the locomotor-activating effects of amphetamine in adult rats that on day 7 had sustained either sham or ibotenic acid lesions of the ventral hippocampus alone ("standard lesions"), or the ventral hippocampus plus surrounding portions of entorhinal cortex and dorsal hippocampus ("large lesions"). "Standard lesions" produced the expected "supersensitive" locomotor response to amphetamine, while "large lesions" did not. No differences between these lesion groups were observed in baseline levels of locomotor activity or habituation. These data suggest that models of enhanced behavioral sensitivity to dopamine agonists after neonatal hippocampal lesions require functionality in the entorhinal cortex and/or dorsal hippocampus. It is possible that the behavioral abnormalities in the "neonatal hippocampal lesion model" reflect, at least in part, aberrant function within spared elements of the hippocampal complex.