COGNITIVE EFFECTS OF NEONATAL HIPPOCAMPAL-LESIONS IN A RAT MODEL OF SCHIZOPHRENIA

Lesioning the ventral hippocampus of neonatal rats has been proposed a s an experimental model of schizophrenia. This lesion causes a syndrom e of hyperresponsivity to the stimulant effects of amphetamine, impair ed grooming and disrupted social interactions, effects that emerge dur ing adolescence, much like schizophrenia. Persisting cognitive effects of neonatal ventral hippocampal lesions were assessed in the current study, because the hippocampus is critically important for a variety o f cognitive impairment and because it is an important feature a of sch izophrenia. Spatial learning and working memory were assessed in the r adial-arm maze, which is sensitive to the adverse effects of hippocamp al lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. D eficits were seen during the prepubertal period as well as in adulthoo d. Even though the lesioned rats performed move poorly, they were sign ificantly less sensitive to the amnestic effects of the nicotinic anta gonist mecamylamine and the muscarinic antagonist scopolamine. No sign ificant effects of nicotine or amphetamine were seen in either the les ioned or control groups. The long-lasting deficits in spatial learning and working memory resulting from neonatal ventral hippocampal lesion s show that, unlike frontal cortical lesions during the same age, the effects of hippocampal lesions are not overcome during development. Th e resistance to the amnestic effects of nicotinic and muscarinic acety lcholine (ACh) antagonists suggests that the hippocampus is a critical site for the action of these drugs. Neonatal hippocampal lesions may provide a good model of the cognitive impairments of schizophrenia and may be useful to assess novel drug effects to counteract the cognitiv e deficits in schizophrenia. (C) 1996 American College of Neuropsychop harmacology