Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia

R. Chambers, Jonathan Moore, Joseph P. McEvoy, Edward D. Levin

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Lesioning the ventral hippocampus of neonatal rats has been proposed as an experimental model of schizophrenia. This lesion causes a syndrome of hyperresponsivity to the stimulant effects of amphetamine, impaired grooming and disrupted social interactions, effects that emerge during 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 of cognitive functions and cognitive impairment and because it is an important feature of schizophrenia. Spatial learning and working memory were assessed in the radial-arm maize, which is sensitive to the adverse effects of hippocampal lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. Deficits were seen during the prepubertal period as well as in adulthood. Even though the lesioned rats performed more poorly, they were significantly less sensitive to the amnestic effects of the effects of the nicotinic antagonist mecamylamine and the muscarinic antagonist scopolamine. No significant effects of nicotine or amphetamine were seen in either the lesioned or control groups. The long-lasting deficits in spatial learning and working memory resulting from neonatal ventral hippocampal lesions show that, unlike frontal cortical lesions during the same age, the effects of hippocampal lesions are not overcome during development. The resistance to the amnestic effects of nicotinic and muscarinic acetylcholine (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 cognitive deficits in schizophrenia.

Original languageEnglish (US)
Pages (from-to)587-594
Number of pages8
JournalNeuropsychopharmacology
Volume15
Issue number6
DOIs
StatePublished - Dec 1996
Externally publishedYes

Fingerprint

Schizophrenia
Hippocampus
Muscarinic Antagonists
Amphetamine
Short-Term Memory
Nicotinic Antagonists
Mecamylamine
Grooming
Scopolamine Hydrobromide
Cholinergic Antagonists
Interpersonal Relations
Nicotine
Pharmaceutical Preparations
Cognition
Zea mays
Theoretical Models
Control Groups
Cognitive Dysfunction
Spatial Memory
Spatial Learning

Keywords

  • Hippocampus
  • Learning
  • Lesion
  • Memory
  • Neonatal
  • Radi al-arm Maze
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia. / Chambers, R.; Moore, Jonathan; McEvoy, Joseph P.; Levin, Edward D.

In: Neuropsychopharmacology, Vol. 15, No. 6, 12.1996, p. 587-594.

Research output: Contribution to journalArticle

Chambers, R. ; Moore, Jonathan ; McEvoy, Joseph P. ; Levin, Edward D. / Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia. In: Neuropsychopharmacology. 1996 ; Vol. 15, No. 6. pp. 587-594.
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