title: The enhanced oral response to the 5-HT2 agonist Ro 60-0175 in parkinsonian rats involves the entopeduncular nucleus: electrophysiological correlates.
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.
authors.affiliation: Unité Mixte de Recherche 5293, Centre National de la Recherche Scientifique, Université Bordeaux, 146, rue Léo Saignat, 33076, Bordeaux Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Lagière
authors.forename: S
authors.initials: S
authors.lastname: Navailles
authors.forename: L
authors.initials: L
authors.lastname: Mignon
authors.forename: A
authors.initials: A
authors.lastname: Roumegous
authors.forename: M-F
authors.initials: MF
authors.lastname: Chesselet
authors.forename: P
authors.initials: P
authors.lastname: De Deurwaerdère
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena / Q000502:physiology; D020392:Entopeduncular Nucleus / Q000187:drug effects* / Q000378:metabolism; D005021:Ethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
chemical_list: D005021:Ethylamines; D007211:Indoles; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D012701:Serotonin
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