Turning behaviour induced by stimulation of the 5-HT receptors in the subthalamic nucleus

The basal ganglia, which receive a rich serotonergic innervation, have been implicated in hyperkinetic and hypokinetic disorders. Moreover, a decrease in subthalamic nucleus (STN) activity has been associated with motor hyperactivity. To address the role of subthalamic serotonergic innervation in its motor function, turning behaviour was studied in rats with stimulation of the subthalamic serotonin (5-HT) receptors by intracerebral microinjections. The intrasubthalamic administration of 5-HT induced dose-dependent contralateral turning behaviour, with a maximal effect at a dose of 2.5 mug in 0.2 muL. Similar results were observed with microinjections of other 5-HT receptor agonists: quipazine (a 5-HT2B/C/3 agonist), MK-212 (a 5-HT2B/C agonist) and m-chlorophenylbiguanidine (a 5-HT3 agonist), while microinjections of 5-HT into the zona incerta or in the previously lesioned STN were ineffective. The effect of 5-HT was blocked by coadministration of the antagonist mianserin. Stimulation of subthalamic 5-HT receptors in animals bearing a lesion of the nigrostriatal pathway did not modify the motor response, which indicates that the dopamine innervation of the nucleus is not involved in this effect. Kainic acid lesion of the substantia nigra pars reticulata (SNr) suppressed the contralateral rotations elicited by stimulation of 5-HT2B/C/3 subthalamic receptors. This suggests a role of the subthalamic-nigral pathway in the turning activity. Furthermore, the partial blockade of glutamatergic receptors in the SNr by the antagonist DNQX increased the contralateral circling elicited by stimulation of 5-HT receptors in the STN. We concluded that the activation of the 5-HT2B/C and 5-HT3 subthalamic receptors elicited contralateral turning behaviour, probably via the subthalamic-nigral pathway.