Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by D2 and 5‐HT1A receptors
- 16 April 2004
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 89 (4) , 834-843
- https://doi.org/10.1111/j.1471-4159.2004.02355.x
Abstract
The present microdialysis study evaluated the anticonvulsant activity of extracellular hippocampal dopamine (DA) and serotonin (5‐HT) with concomitant assessment of the possible mutual interactions between these monoamines. The anticonvulsant effects of intrahippocampally applied DA and 5‐HT concentrations were evaluated against pilocarpine‐induced seizures in conscious rats. DA or 5‐HT perfusions protected the rats from limbic seizures as long as extracellular DA or 5‐HT concentrations ranged, respectively, between 70–400% and 80–350% increases compared with the baseline levels. Co‐perfusion with the selective D2 blocker remoxipride or the selective 5‐HT1A blocker WAY‐100635 clearly abolished all anticonvulsant effects. These anticonvulsant effects were mediated independently since no mutual 5‐HT and DA interactions were observed as long as extracellular DA and 5‐HT levels remained within these protective ranges. Simultaneous D2 and 5‐HT1A receptor blockade significantly aggravated pilocarpine‐induced seizures. High extracellular DA (> 1000% increases) or 5‐HT (> 900% increases) concentrations also worsened seizure outcome. The latter proconvulsive effects were associated with significant increases in extracellular glutamate (Glu) and mutual increases in extracellular monoamines. Our results suggest that, within a certain concentration range, DA and 5‐HT contribute independently to the prevention of hippocampal epileptogenesis via, respectively, D2 and 5‐HT1A receptor activation.Keywords
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