Selective blockade of serotonin2C receptor enhances Fos expression specifically in the striatum and the subthalamic nucleus within the basal ganglia

Serotonin2C (5-HT2C) receptors are widely expressed in the basal ganglia, a group of brain regions involved in the control of motor behavior. However, it remains unclear whether their tonic influence on neuronal activity is distributed in these regions. We have addressed this question by measuring the product of the proto-oncogene c-Fos in rats after peripheral administration of the non-selective 5-HT antagonist mianserin, the 5-HT2C/2B antagonist SER-082 or the selective 5-HT2C antagonist SB 243213. The intraperitoneal administration of 1 mg/kg of SB 243213 or SER-082, but not mianserin, enhanced Fos-immunoreactive cells in the subthalamic nucleus and the striatum, primarily its medial portion. None of these treatments significantly affected Fos expression in the external globus pallidus, the entopeduncular nucleus (the internal globus pallidus in primate) or the substantia nigra pars reticulata. The data suggest that selective blockade of 5-HT2C receptors is necessary to unmask a tonic regulation of neuronal activity by this receptor in the basal ganglia and that this effect is restricted to the two structures receiving cortical entries, the striatum and the subthalamic nucleus.