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In vivo modulatory action of extracellular glutamate on the anticonvulsant effects of hippocampal dopamine and serotonin.
Epilepsia. 2005 Jun; 46(6):828-36.E

Abstract

PURPOSE

Our recent work (Clinckers et al., J Neurochem 2004;89:834-43) demonstrated that intrahippocampal perfusion of 2 nM dopamine or serotonin via a microdialysis probe offered complete protection against focal pilocarpine-induced limbic seizures and did not influence basal extracellular hippocampal glutamate levels. Ten nanomolar dopamine or serotonin perfusion, however, worsened seizures and was accompanied by significant extracellular glutamate increases to approximately 200%. The significance of these glutamate elevations in seizure generation remains unclear. The present microdialysis study investigated the modulatory role of extracellular hippocampal glutamate levels in these monoaminergic protective and proconvulsant effects.

METHODS

A first group of male Wistar albino rats was perfused intrahippocampally for 240 min with 6.25 microM glutamate alone to increase extracellular levels by 200%. Other animals were perfused with anticonvulsant concentrations of monoamines throughout the experiments while receiving continuous coperfusions of 6.25 microM glutamate either before, during, and after (240 min) or only after (100 min) pilocarpine perfusion (40 min). Rats were scored for epileptic behavior, and the mean scores were compared with those of the control group. Microdialysates were analyzed for monoamine and glutamate content with microbore liquid chromatography.

RESULTS

No convulsions occurred during glutamate perfusion alone. When monoamines and glutamate were coperfused before pilocarpine administration, the anticonvulsant effect of the monoamines was lost. Glutamate addition after pilocarpine administration did not affect monoaminergic seizure protection.

CONCLUSIONS

These results indicate that extracellular glutamate increases per se do not necessarily induce seizures but that they can modulate the anticonvulsant effects exerted by hippocampal monoamines.

Authors+Show Affiliations

Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15946324

Citation

Clinckers, Ralph, et al. "In Vivo Modulatory Action of Extracellular Glutamate On the Anticonvulsant Effects of Hippocampal Dopamine and Serotonin." Epilepsia, vol. 46, no. 6, 2005, pp. 828-36.
Clinckers R, Gheuens S, Smolders I, et al. In vivo modulatory action of extracellular glutamate on the anticonvulsant effects of hippocampal dopamine and serotonin. Epilepsia. 2005;46(6):828-36.
Clinckers, R., Gheuens, S., Smolders, I., Meurs, A., Ebinger, G., & Michotte, Y. (2005). In vivo modulatory action of extracellular glutamate on the anticonvulsant effects of hippocampal dopamine and serotonin. Epilepsia, 46(6), 828-36.
Clinckers R, et al. In Vivo Modulatory Action of Extracellular Glutamate On the Anticonvulsant Effects of Hippocampal Dopamine and Serotonin. Epilepsia. 2005;46(6):828-36. PubMed PMID: 15946324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo modulatory action of extracellular glutamate on the anticonvulsant effects of hippocampal dopamine and serotonin. AU - Clinckers,Ralph, AU - Gheuens,Sarah, AU - Smolders,Ilse, AU - Meurs,Alfred, AU - Ebinger,Guy, AU - Michotte,Yvette, PY - 2005/6/11/pubmed PY - 2005/7/1/medline PY - 2005/6/11/entrez SP - 828 EP - 36 JF - Epilepsia JO - Epilepsia VL - 46 IS - 6 N2 - PURPOSE: Our recent work (Clinckers et al., J Neurochem 2004;89:834-43) demonstrated that intrahippocampal perfusion of 2 nM dopamine or serotonin via a microdialysis probe offered complete protection against focal pilocarpine-induced limbic seizures and did not influence basal extracellular hippocampal glutamate levels. Ten nanomolar dopamine or serotonin perfusion, however, worsened seizures and was accompanied by significant extracellular glutamate increases to approximately 200%. The significance of these glutamate elevations in seizure generation remains unclear. The present microdialysis study investigated the modulatory role of extracellular hippocampal glutamate levels in these monoaminergic protective and proconvulsant effects. METHODS: A first group of male Wistar albino rats was perfused intrahippocampally for 240 min with 6.25 microM glutamate alone to increase extracellular levels by 200%. Other animals were perfused with anticonvulsant concentrations of monoamines throughout the experiments while receiving continuous coperfusions of 6.25 microM glutamate either before, during, and after (240 min) or only after (100 min) pilocarpine perfusion (40 min). Rats were scored for epileptic behavior, and the mean scores were compared with those of the control group. Microdialysates were analyzed for monoamine and glutamate content with microbore liquid chromatography. RESULTS: No convulsions occurred during glutamate perfusion alone. When monoamines and glutamate were coperfused before pilocarpine administration, the anticonvulsant effect of the monoamines was lost. Glutamate addition after pilocarpine administration did not affect monoaminergic seizure protection. CONCLUSIONS: These results indicate that extracellular glutamate increases per se do not necessarily induce seizures but that they can modulate the anticonvulsant effects exerted by hippocampal monoamines. SN - 0013-9580 UR - https://www.unboundmedicine.com/medline/citation/15946324/In_vivo_modulatory_action_of_extracellular_glutamate_on_the_anticonvulsant_effects_of_hippocampal_dopamine_and_serotonin_ L2 - https://doi.org/10.1111/j.1528-1167.2005.57004.x DB - PRIME DP - Unbound Medicine ER -