| Abstract No.: | B-C2085 |
| Country: | Canada |
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| Title: | PERINATAL ADMINISTRATION OF LOW-DOSE DOMOIC ACID ALTERS CENTRAL NERVOUS SYSTEM EXCITABILITY IN THE ADULT RAT |
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| Authors/Affiliations: | 2 Daphne Gill*; 1 Jesper Bastlund; 2 R. Andrew Tasker;
1 H. Lundbeck A/S, Copenhagen, Denmark; 2 University of Prince Edward Island, PEI, Canada
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| Content: | We have previously shown that systemic perinatal administration of low-dose (20µg/kg) domoic acid (DOM) results in alterations in adult rats that may be manifested behaviourally as low-grade seizure (Doucette et al., 2004) or at the cellular level in area CA-3 and the dentate gyrus in the hippocampus (Bernard et al, 2005). To further these investigations we used implantable radio telemetry to record electrocorticographical (ECoG) outputs during the seizure-like behaviour. Subsequently, rats were exposed to a very low dose of pentylenetetrazol (PTZ) to assess non-convulsive waveform generation. To investigate focal seizure threshold, as well as overall seizure propagation, a separate group of rats were implanted with microelectrodes and studied using a standard amygdala kindling paradigm. Domoate treated rats showed a significant increase in overall brain wave activity during the seizure-like behaviours that can be visualized as alterations in electroencephalographic (EEG) tracings, as well as a lower generalized seizure threshold in response to PTZ administration (p=0.021). Amygdala kindled DOM rats also had a significantly reduced seizure threshold (p=0.013), but did not display significant alterations in overall seizure propagation. We conclude that early DOM administration lowers both generalized and focal seizure thresholds, and results in alterations in cortical EEG in adulthood, indicating that the perinatal drug treatment results in long-term changes in excitatory and/or inhibitory tone in the brain.
Supported by the Atlantic Innovation Fund & an NSERC Industrial Post-graduate Scholarship to D.A.G.
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