Comparative behavioural toxicity of domoic acid and kainic acid in neonatal rats

• Published in: Neurotoxicology and teratology Vol. 22; no. 6; pp. 863 - 869
• Main Authors: Doucette, T.A, Strain, S.M, Allen, G.V, Ryan, C.L, Tasker, R.A.R
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2000; Elsevier Science
• Subjects: Animals; Animals, Newborn; Behavior, Animal - drug effects; Behaviour; Biological and medical sciences; Development; Domoic acid; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Excitatory amino acid; Female; Glutamate; Kainic acid; Kainic Acid - analogs & derivatives; Kainic Acid - toxicity; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Toxicity: nervous system and muscle; Development; Excitatory amino acid; Behaviour; Glutamate; Domoic acid; Kainic acid; Nervous system diseases; Intraperitoneal administration; Toxicity; Developmental disorder; Glutamate receptor; Behavioral disorder; Dose activity relation; Spontaneous physical activity; Newborn animal; Excitatory aminoacid; Behavior; Age
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/S0892-0362(00)00110-0

Cumulative behavioural toxicity was measured in groups of male and female rat pups ( n=6/sex) at different stages of postnatal development. Dose–response curves (DRCs) for toxicity produced by domoic acid (DOM) were generated using animals on postnatal days (PND) 0, 5, 14, and 22, using a behavioural rating scale. In a subsequent experiment, DRCs for toxicity generated by either DOM or kainic acid were produced in rats at PND 8 and 14 for comparison between the two toxins. DOM was found to be a very potent neurotoxin in newborn rats and the potency of DOM progressively decreased with increasing age (interpolated ED 50=0.12, 0.15, 0.30, and 1.06 mg/kg at PND 0, 5, 14, and 22, respectively). In addition, the patterns of behavioural expression were found to differ with age. Comparisons between DOM and kainic acid revealed that DOM was approximately six-fold more potent than kainate at both PND 8 and PND 14 and that both toxins were approximately two-fold less potent in PND 14 rats, compared to PND 8. This implies that the mechanism(s) responsible for reduced potency is/are similar between the two compounds. Consistent with previous reports, however, there were both similarities and differences in the observed patterns of behavioural toxicity produced by the two toxins at both ages.