Morphine differentially affects domoic acid and kainic acid toxicity in vivo

The effect of systemic injections of morphine on behavioural toxicity and hippocampal (CA3 region) damage produced by both domoic and kainic acids was investigated in mice. Low doses of morphine (2.0 and 4.0 mg kg-1), but not higher doses, significantly antagonized the toxic response to a previously determined TD50 of domoic acid. By contrast, low doses of morphine had either minimal or no effect on the response to an equitoxic dose of kainic acid (TD50), but higher doses (6.0 and 8.0 mg kg-1) resulted in significant potentiation of kainate toxicity. These results provide the first evidence of a pharmacological dissociation between the mechanisms of domoic acid and kainic acid toxicity in vivo, suggesting that these two toxins produce behavioural and hippocampal toxicity via overlapping but non-identical mechanisms.