Cognitive, Behavioral, and Systems NeuroscienceResearch PaperStimulation of serotonin2C receptors elicits abnormal oral movements by acting on pathways other than the sensorimotor one in the rat basal ganglia
Section snippets
Animals
Male Sprague–Dawley rats (Charles River, Lyon, France) weighing 330–380 g were used. Animals were kept at constant room temperature (21±2 °C) and relative humidity (60%) with a 12-light/dark cycle (dark from 8 pm) and had free access to water and food. All animal use procedures conformed to International European Ethical Standards (86/609-EEC) and the French National Committee (décret 87/848) for the care and use of laboratory animals. All efforts were made to minimize animal suffering and to
Oral movements induced by peripheral administration of Ro-60-0175: role of 5-HT2C receptors
I.p. injection of 1 mg/kg of Ro-60-0175 elicited a significant increase in oral bouts [P<0.001 after a significant one-way ANOVA; Fig. 1]. The incidence of oral bouts was maximal 40-min after the injection of the drug (Inset Fig. 1). The effect of Ro-60-0175 slowly decreased without reaching control values 1 h after its administration. Its effect has been studied in the presence of the 5-HT2C antagonist SB-243213 (1 mg/kg), administered i.p. 1-h before Ro-60-0175. SB-243213, without effect by
Discussion
The present study was undertaken to determine the extent to which the abnormal orofacial movements induced by 5-HT2C receptor stimulation affects the sensorimotor parts within basal ganglia. Our results provide evidence that 5-HT2C receptor stimulation induces orofacial dyskinesia independently from molecular or electrophysiological changes along the sensorimotor pathway. Rather, they suggest that 5-HT2C agonists act preferentially within the associative and limbic territories of basal ganglia.
Conclusion
In conclusion, this work is the first to demonstrate that abnormal orofacial movements elicited by a 5-HT2C receptor agonist is not directly related to changes of activity in the sensorimotor territories of basal ganglia, and would rather correspond to the involvement of the associative/limbic territories.
Acknowledgments
This work was supported by grants from Centre National de la Recherche Scientifique and Bordeaux 2 University. We are grateful to Dr. M. Wood (Psychiatry CEDD, GlaxoSmithKline, Harlow, UK) and Dr. P Weber (Hoffman-LaRoche, Bale, Switzerland) for the generous gift of SB-243213 and Ro-60-0175, respectively. The authors wish to thank Dr. M. Lucas and Dr. B. Ballion for technical support and Dr. Martin Guthrie for correcting English language.
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