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Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y

(2007) EUROPEAN JOURNAL OF NEUROSCIENCE. 26(11). p.3079-3092
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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.
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

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Chicago
Meurs, Alfred, Ralph Clinckers, Guy Ebinger, Yvette Michotte, and Ilse Smolders. 2007. “Sigma 1 Receptor-mediated Increase in Hippocampal Extracellular Dopamine Contributes to the Mechanism of the Anticonvulsant Action of Neuropeptide Y.” European Journal of Neuroscience 26 (11): 3079–3092.
APA
Meurs, A., Clinckers, R., Ebinger, G., Michotte, Y., & Smolders, I. (2007). Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y. EUROPEAN JOURNAL OF NEUROSCIENCE, 26(11), 3079–3092.
Vancouver
1.
Meurs A, Clinckers R, Ebinger G, Michotte Y, Smolders I. Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y. EUROPEAN JOURNAL OF NEUROSCIENCE. 2007;26(11):3079–92.
MLA
Meurs, Alfred, Ralph Clinckers, Guy Ebinger, et al. “Sigma 1 Receptor-mediated Increase in Hippocampal Extracellular Dopamine Contributes to the Mechanism of the Anticonvulsant Action of Neuropeptide Y.” EUROPEAN JOURNAL OF NEUROSCIENCE 26.11 (2007): 3079–3092. Print.
@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},
  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://dx.doi.org/10.1111/j.1460-9568.2007.05911.x},
  volume       = {26},
  year         = {2007},
}

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