@article{7154032,
  abstract     = {{The potent anticonvulsant properties of neuropeptide Y (NPY) are generally attributed to a Y-2 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 D-2 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 Y-2 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 D-2 receptor antagonist remoxipride, the Y-2 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 mu L) and intrahippocampal (20-50 mu M) NPY administration increased hippocampal dopamine and attenuated pilocarpine-induced seizures. Hippocampal D-2 receptor blockade (4 mu M remoxipride) reversed the anticonvulsant effect of NPY. Y-2 receptor blockade (1 mu M BIIE0246) reversed the anticonvulsant effect of NPY but did not prevent NPY-induced increases in hippocampal dopamine. Sigma 1 receptor blockade (10 mu M 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 D-2 receptors. This novel mechanism of anticonvulsant action of NPY is separate from, and may be complementary to, the well established Y-2 receptor-mediated inhibition of hippocampal excitability.}},
  author       = {{Meurs, Alfred and Clinckers, Ralph and Ebinger, Guy and Michotte, Yvette and Smolders, Ilse}},
  issn         = {{0953-816X}},
  journal      = {{EUROPEAN JOURNAL OF NEUROSCIENCE}},
  keywords     = {{microdialysis,hippocampus,rat,seizure,METHYL-D-ASPARTATE,SUPPRESSES EPILEPTIFORM ACTIVITY,INDUCED LIMBIC SEIZURES,SIGMA-RECEPTOR LIGANDS,INDUCED MOTOR SEIZURES,RAT FRONTAL-CORTEX,WET DOG SHAKES,IN-VITRO,PEPTIDE-YY,GLUTAMATE RELEASE}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{3079--3092}},
  title        = {{Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y}},
  url          = {{http://doi.org/10.1111/j.1460-9568.2007.05911.x}},
  volume       = {{26}},
  year         = {{2007}},
}

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