Linked Life Data

18005069

Source:http://linkedlifedata.com/resource/pubmed/id/18005069

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-11-21
pubmed:abstractText
The potent anticonvulsant properties of neuropeptide Y (NPY) are generally attributed to a Y2 receptor-mediated inhibition of glutamatergic synaptic transmission. Independent studies have shown that NPY increases brain dopamine content, possibly via interaction with sigma 1 receptors. Recently, we showed that increased extracellular hippocampal dopamine attenuates pilocarpine-induced limbic seizures via activation of hippocampal D2 receptors. Our aim in this study was to elucidate the role of increased hippocampal dopamine in the mechanism of the anticonvulsant action of NPY and to investigate the involvement of Y2 and sigma 1 receptors in this process. Limbic seizures were evoked in freely moving rats by intrahippocampal administration of pilocarpine via a microdialysis probe. NPY was administered intracerebroventricularly, intrahippocampally via the microdialysis probe, or coadministered intrahippocampally with the D2 receptor antagonist remoxipride, the Y2 receptor antagonist BIIE0246 or the sigma 1 receptor antagonist BD1047. Changes in hippocampal extracellular dopamine were monitored, and behavioural changes indicative of seizure activity were scored. Intracerebroventricular (10 nmol/3 microL) and intrahippocampal (20-50 microm) NPY administration increased hippocampal dopamine and attenuated pilocarpine-induced seizures. Hippocampal D2 receptor blockade (4 microm remoxipride) reversed the anticonvulsant effect of NPY. Y2 receptor blockade (1 microm BIIE0246) reversed the anticonvulsant effect of NPY but did not prevent NPY-induced increases in hippocampal dopamine. Sigma 1 receptor blockade (10 microm BD1047) abolished NPY-induced increases in hippocampal dopamine and reversed the anticonvulsant effect of NPY. Our results indicate that NPY-induced increases in hippocampal dopamine are mediated via sigma 1 receptors and contribute to the anticonvulsant effect of NPY via increased activation of hippocampal D2 receptors. This novel mechanism of anticonvulsant action of NPY is separate from, and may be complementary to, the well established Y2 receptor-mediated inhibition of hippocampal excitability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3079-92
pubmed:meshHeading
pubmed-meshheading:18005069-Analysis of Variance, pubmed-meshheading:18005069-Animals, pubmed-meshheading:18005069-Anticonvulsants, pubmed-meshheading:18005069-Behavior, Animal, pubmed-meshheading:18005069-Chromatography, High Pressure Liquid, pubmed-meshheading:18005069-Disease Models, Animal, pubmed-meshheading:18005069-Dopamine, pubmed-meshheading:18005069-Dopamine Antagonists, pubmed-meshheading:18005069-Dose-Response Relationship, Drug, pubmed-meshheading:18005069-Epilepsy, pubmed-meshheading:18005069-Ethylenediamines, pubmed-meshheading:18005069-Hippocampus, pubmed-meshheading:18005069-Male, pubmed-meshheading:18005069-Microdialysis, pubmed-meshheading:18005069-Neuropeptide Y, pubmed-meshheading:18005069-Pilocarpine, pubmed-meshheading:18005069-Rats, pubmed-meshheading:18005069-Rats, Wistar, pubmed-meshheading:18005069-Receptors, sigma, pubmed-meshheading:18005069-Remoxipride, pubmed-meshheading:18005069-Severity of Illness Index, pubmed-meshheading:18005069-Time Factors
pubmed:year
2007
pubmed:articleTitle
Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y.
pubmed:affiliation
Department of Neurology, U. Z. Brussel, Laarbeeklaan 101,1090 Brussels, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't