Strain and colony differences in the neurotoxic sequelae of MK-801 visualized with the amino-cupric-silver method

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2003-11, Vol.55 (4), p.287-294
• Main Authors: Bueno, Adrian, de Olmos, Soledad, Manzini, Fernando, Desmond, Nancy L., de Olmos, Jose
• Format: Article
• Language: English
• Subjects: amino-cupric-silver technique; amygdala; Anatomy; Animals; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain Diseases - chemically induced; Brain Diseases - genetics; Brain Diseases - pathology; Central nervous system; Copper; Disease Models, Animal; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - toxicity; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - toxicity; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; hippocampus; intrastrain difference; neocortex; Nerve Degeneration - chemically induced; Nerve Degeneration - genetics; Nerve Degeneration - pathology; neurodegeneration; NMDA receptor antagonist; olfactory system; Rats; Rats, Sprague-Dawley - genetics; Rats, Wistar - genetics; Silver; Species Specificity; Sprague Dawley rat; Staining and Labeling - methods; Strain difference; Vertebrates: nervous system and sense organs; Wistar rat
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1078/0940-2993-00327

The strain and sex of a species under investigation may influence the animal's physiological response to a variety of stimuli. Strain and sex differences are important considerations when evaluating animal models. In the rodent MK-801 model of schizophrenia, degenerative changes occur widely in the main olfactory system and in a number of cortical brain regions. In the present report, we compare the effects of MK-801 neurotoxicity in two strains of female rats and also two lines within each strain. The magnitude and regional extent of the neurodegeneration detected with the amino-cupric-silver method varied markedly both between the Sprague-Dawley and Wistar rat strains and also between two lines derived from each strain. For example, terminal degeneration occurred in layer VI of somatosensory cortex and the central extended amygdala in Sprague-Dawley but not Wistar rats. Moreover, MK-801 treatment led to somatodendritic degeneration in the dentate gyrus of the dorsal hippocampus and basolateral amygdala in Wistar rats from Charles River Laboratories but not those from Ferreyra Institute. There are thus both strain and intrastrain differences in the magnitude of the neurodegenerative response to MK-801 treatment. The differing neurotoxicity of MK-801 between rat strains and between lines within a strain may reflect genetic variation and/or differences in hepatic biotransformation and thus the bioavailability of the drug between strains and lines within a strain.