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The enhanced oral response to the 5-HT2 agonist Ro 60-0175 in parkinsonian rats involves the entopeduncular nucleus: electrophysiological correlates

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Abstract

Lesions of nigrostriatal dopaminergic neurons as seen in Parkinson’s disease (PD) increase orofacial responses to serotonergic (5-HT) agonists in rodents. Although this response to 5-HT agonists has been related to aberrant signalling in the basal ganglia, a group a subcortical structures involved in the control of motor behaviours, it deserves additional studies with respect to the specific loci involved. Using measurements of orofacial activity, as well as single-cell recordings in vivo, we have studied the role of the entopeduncular nucleus (EPN; equivalent to the internal globus pallidus of primates), an output structure of basal ganglia, in the hypersensitized responses to a 5-HT agonist in sham- or unilaterally dopamine-depleted rats. Intra-EPN injections of Ro 60-0175 (0.3 and 1 μg/100 nl) promoted robust oral movements in 6-OHDA rats without affecting oral activity in sham-depleted rats. Peripheral administration of Ro 60-0175 (3 mg/kg ip) decreased EPN neuronal firing rate in 6-OHDA rats compared to sham-depleted rats. Such an effect was also observed when the agonist (0.2 μg/20 nl) was locally applied onto EPN neurons. These data demonstrate the contribution of EPN to hypersensitized responses to 5-HT agonists in a rat model of PD.

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Abbreviations

5-HT:

Serotonin

5-HT2C :

Serotonin(2C) Receptors

SNr:

Substantia nigra pars reticulata

SNc:

Substantia nigra pars compacta

EPN:

Entopeduncular nucleus

DA:

Dopamine

6-OHDA:

6-Hydroxydopamine

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Acknowledgments

This work was supported by Public Health Service Grants R37-MH44894 and P50-NS 38367, “Centre National de la Recherche Scientifique” and Bordeaux 2 University. Travelling facilities for Professor P De Deurwaerdère were supported by the European cooperation in science and technology (COST action CM1103). Mélanie Lagière is a fellowship recipient from the Ministère de la Recherche et de l’Enseignement Supérieur. The authors wish to thank Dr M. Guthrie for linguistic assistance and Vincent Proton for technical assistance.

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Authors and Affiliations

  1. Unité Mixte de Recherche 5293, Centre National de la Recherche Scientifique, Université Bordeaux, 146, rue Léo Saignat, 33076, Bordeaux Cedex, France

    M. Lagière, S. Navailles, A. Roumegous & P. De Deurwaerdère

  2. Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095-1769, USA

    L. Mignon & M.-F. Chesselet

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  1. M. Lagière
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  2. S. Navailles
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  3. L. Mignon
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  4. A. Roumegous
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  5. M.-F. Chesselet
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  6. P. De Deurwaerdère
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Correspondence to P. De Deurwaerdère.

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Lagière, M., Navailles, S., Mignon, L. et al. The enhanced oral response to the 5-HT2 agonist Ro 60-0175 in parkinsonian rats involves the entopeduncular nucleus: electrophysiological correlates. Exp Brain Res 230, 513–524 (2013). https://doi.org/10.1007/s00221-013-3478-4

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  • DOI: https://doi.org/10.1007/s00221-013-3478-4

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