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S M Strain

Publications and source records attributed to S M Strain.

20 records · Page 2Linked to original sources
PubMedDate not supplied

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

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.

Animals↗
PubMedDate not supplied

Synergism between NMDA and domoic acid in a murine model of behavioural neurotoxicity.

We have examined the behavioural neurotoxicity of domoic acid (DOM) and kainic acid (KA) in mice following administration of ligands active at the N-methyl-d-aspartate (NMDA) receptor. Groups of female CD-1 mice (n=4) were injected i.p. with saline or one of three doses of either DOM or KA. Doses of DOM and KA were selected from the steep portion of the respective dose response curves and were equitoxic when compared between the two ligands. Toxicity was recorded as both total cumulative toxicity over 60 min according to a previously validated 7 point rating scale, and as the latency to the onset of tremors and/or convulsions. Five minutes prior to administration of either agonist mice were injected with either saline, NMDA (40 mg/kg) or a combination of NMDA and 15 mg/kg CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid). Neither NMDA nor CPP at these doses produced significant changes from baseline responding when injected prior to saline. Injection of NMDA prior to DOM, however, resulted in significantly increased cumulative toxicity and significantly reduced latencies to seizures at the two highest doses of DOM (3.75 and 5.0 mg/kg). NMDA-induced potentiation of DOM toxicity was completely antagonized by co-administration of CPP. In contrast, injection of NMDA prior to KA did not result in significant changes in KA toxicity at any of the doses tested using either index of behavioural toxicity. These results confirm previous reports of synergism between DOM and ligands acting at the NMDA receptor in isolated neurons, and provide further evidence of pharmacological dissociation of the actions of DOM and KA in vivo.

Animals↗