STIMULATION OF SEROTONIN2C RECEPTORS ELICITS ABNORMAL ORAL MOVEMENTS BY ACTING ON PATHWAYS OTHER THAN THE SENSORIMOTOR ONE IN THE RAT BASAL GANGLIA
Neuroscience. 2010-08-01; 169(1): 158-170
DOI: 10.1016/j.neuroscience.2010.04.061
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Serotonin2C (5-HT(2C)) receptors act in the basal ganglia, a group of
sub-cortical structures involved in motor behavior, where they are thought to
modulate oral activity and participate in iatrogenic motor side-effects in
Parkinson’s disease and Schizophrenia. Whether abnormal movements initiated by
5-HT(2C) receptors are directly consequent to dysfunctions of the motor circuit
is uncertain. In the present study, we combined behavioral, immunohistochemical
and extracellular single-cell recordings approaches in rats to investigate the
effect of the 5-HT(2C) agonist Ro-60-0175 respectively on orofacial dyskinesia,
the expression of the marker of neuronal activity c-Fos in basal ganglia and the
electrophysiological activity of substantia nigra pars reticulata (SNr) neuron
connected to the orofacial motor cortex (OfMC) or the medial prefrontal cortex
(mPFC). The results show that Ro-60-0175 (1 mg/kg) caused bouts of orofacial
movements that were suppressed by the 5-HT(2C) antagonist SB-243213 (1 mg/kg).
Ro-60-0175 (0.3, 1, 3 mg/kg) dose-dependently enhanced Fos expression in the
striatum and the nucleus accumbens. At the highest dose, it enhanced Fos
expression in the subthalamic nucleus, the SNr and the entopeduncular nucleus but
not in the external globus pallidus. However, the effect of Ro-60-0175 was mainly
associated with associative/limbic regions of basal ganglia whereas subregions of
basal ganglia corresponding to sensorimotor territories were devoid of Fos
labeling. Ro-60-0175 (1-3 mg/kg) did not affect the electrophysiological activity
of SNr neurons connected to the OfMC nor their excitatory-inhibitory-excitatory
responses to the OfMC electrical stimulation. Conversely, Ro-60-0175 (1 mg/kg)
enhanced the late excitatory response of SNr neurons evoked by the mPFC
electrical stimulation. These results suggest that oral dyskinesia induced by
5-HT(2C) agonists are not restricted to aberrant signalling in the orofacial
motor circuit and demonstrate discrete modifications in associative territories.