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Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by D 2 and 5‐HT 1A receptors
Author(s) -
Clinckers Ralph,
Smolders Ilse,
Meurs Alfred,
Ebinger Guy,
Michotte Yvette
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02355.x
Subject(s) - microdialysis , serotonin , anticonvulsant , 5 ht receptor , extracellular , dopamine , pilocarpine , chemistry , neurotransmitter , epileptogenesis , pharmacology , monoamine neurotransmitter , hippocampal formation , medicine , endocrinology , receptor , epilepsy , neuroscience , psychology , biochemistry
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 D 2 blocker remoxipride or the selective 5‐HT 1A 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 D 2 and 5‐HT 1A 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, D 2 and 5‐HT 1A receptor activation.