Domoic acid, the alleged "mussel toxin," might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the dorsal hippocampus.

Domoic acid, an excitatory amino acid structurally related to kainate, was recently identified as being presumably responsible for the recent severe intoxication presented by more than 100 people having eaten mussels grown in Prince Edward Island (Canada). The amino acid kainate has been shown to be highly neurotoxic to the hippocampus, which is the most sensitive structure in the central nervous system. The present in vivo electrophysiological studies were undertaken to determine if domoic acid exerts its neurotoxic effect via kainate receptor activation. Unitary extracellular recordings were obtained from pyramidal neurons of the CA1 and the CA3 regions of the rat dorsal hippocampus. The excitatory effect of domoic acid applied by microiontophoresis was compared with that of agonists of the three subtypes of glutamatergic receptors: kainate, quisqualate, and N-methyl-D-aspartate. In CA1, the activation induced by domoic acid was about threefold greater than that induced by kainate; identical concentrations and similar currents were used. In CA3, domoic acid was also three times more potent than kainate. However, the most striking finding was that domoic acid, similar to kainate, was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with quisqualate and N-methyl-D-aspartate. As the differential regional response of CA1 and CA3 pyramidal neurons to kainate is attributable to the extremely high density of kainate receptors in the CA3 region, these results provide the first electrophysiological evidence that domoic acid may produce its neurotoxic effects through kainate receptor activation.

[1]  G. Aghajanian,et al.  Lysergic acid diethylamide and serotonin: a comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. , 1974, The Journal of pharmacology and experimental therapeutics.

[2]  H. Shinozaki,et al.  Effects of kainic acid analogues on crayfish opener muscle , 1976, Neuropharmacology.

[3]  H. Shinozaki,et al.  Inhibition of quisqualate responses by domoic or kainic acid in crayfish opener muscle , 1976, Brain Research.

[4]  K. E. Moore,et al.  A histological study of kainic acid-induced lesions in the rat brain , 1978, Brain Research.

[5]  J. Coyle,et al.  Structure-activity relations for the neurotoxicity of kainic acid derivatives and glutamate analogues , 1978, Neuropharmacology.

[6]  D. Prince,et al.  Cellular and field potential properties of epileptogenic hippocampal slices , 1978, Brain Research.

[7]  J. Olney,et al.  Acute dendrotoxic changes in the hippocampus of kainate treated rats , 1979, Brain Research.

[8]  B. Twitchin,et al.  ACTION OF THE NEUROTOXIN KAINIC ACID ON HIGH AFFINITY UPTAKE OF l‐GLUTAMIC ACID IN RAT BRAIN SLICES , 1979, Journal of neurochemistry.

[9]  Y. Ben‐Ari,et al.  A new model of focal status epilepticus: intra-amygdaloid application of kainic acid elicits repetitive secondarily generalized convulsive seizures , 1979, Brain Research.

[10]  R. C. Collins,et al.  Cerebral metabolic response to systemic kainic acid: 14-C-deoxyglucose studies. , 1980, Life sciences.

[11]  J. Price,et al.  Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: A histological study , 1980, Neuroscience.

[12]  R. C. Collins,et al.  Kainic acid‐induced limbic seizures , 1981, Neurology.

[13]  S. Deadwyler,et al.  Kainic acid produces depolarization of CA3 pyramidal cells in the in vitro hippocampal slice , 1981, Brain Research.

[14]  C. Montigny,et al.  Differential excitatory effects of kainic acid on CA3 and CA1 hippocampal pyramidal neurons: further evidence for the excitotoxic hypothesis and for a receptor-mediated action. , 1981 .

[15]  J. Coyle,et al.  Excitatory amino acid analogues: Neurotoxicity and seizures , 1982, Neuropharmacology.

[16]  J. Coyle,et al.  Kainic acid: insights from a neurotoxin into the pathophysiology of Huntington's disease. , 1983, Neurobehavioral toxicology and teratology.

[17]  T. Takemoto,et al.  Effects of α-kainic acid, domoic acid and their derivatives on a molluscan giant neuron sensitive to β-hydroxy-l-glutamic acid , 1984 .

[18]  J. Kirkpatrick,et al.  A comparison of the effect of kainate and some related amino acids on locomotor activity in cockroaches and electrical activity recorded from locust ventral nerve cord. , 1984, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[19]  S. Nelson,et al.  Attenuation of cerebral glucose use in kainic acid-treated rats by diazepam. , 1987, European journal of pharmacology.

[20]  John M. Walker,et al.  Biologically active compounds from diatoms , 1990 .

[21]  R. Sutherland,et al.  Domoic acid, an environmental toxin, produces hippocampal damage and severe memory impairment , 1990, Neuroscience Letters.

[22]  W. Freed,et al.  Effect of nifedipine and anticonvulsants of kainic acid-induced seizures in mice , 1990, Brain Research.

[23]  T. Perl,et al.  An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. , 1990, The New England journal of medicine.

[24]  M. S. Nijjar,et al.  Relationship between domoic acid levels in the blue mussel (Mytilus edulis) and toxicity in mice. , 1990, Toxicon : official journal of the International Society on Toxinology.

[25]  R. Zatorre,et al.  Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. , 1990, The New England journal of medicine.

[26]  J. Olney,et al.  Domoic acid: A dementia-inducing excitotoxic food poison with kainic acid receptor specificity , 1990, Experimental Neurology.

[27]  R. Tasker,et al.  High-performance liquid chromatographic assay for domoic acid in serum of different species. , 1990, Journal of chromatography.