Subthalamic high frequency stimulation induced rotations are differentially mediated by D1 and D2 receptors
Neuropharmacology. 2004-06-01; 46(7): 974-983
DOI: 10.1016/j.neuropharm.2004.01.007
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1. Neuropharmacology. 2004 Jun;46(7):974-83.
Subthalamic high frequency stimulation induced rotations are differentially
mediated by D1 and D2 receptors.
Bergmann O(1), Winter C, Meissner W, Harnack D, Kupsch A, Morgenstern R, Reum T.
Author information:
(1)Institute of Pharmacology and Toxicology, Charité Campus Mitte, Humboldt
University, Berlin, Germany.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) has clinically
emerged as a promising approach in the treatment of Parkinson’s disease,
epilepsy, dystonia as well as compulsive and possibly other mood disorders. The
underlying mechanisms are incompletely understood, but are definitely related to
high frequency and likely to involve the dopamine (DA)-system. To further test
this hypothesis the present study investigated the modulation of STN-HFS-induced
circling by systemic and intracerebral injection of drugs acting on DA receptors
in naive freely moving rats. Within this experimental setup, unilateral STN-HFS
alone induced intensity-dependent circling. Systemic injections of selective D1-
(SCH-23390) and D2-((-)-sulpiride) antagonists as well as the mixed D1 and D2
agonist apomorphine dose-dependently reduced STN-HFS-induced rotational behavior.
Intracerebral microinjections of (-)-sulpiride but not SCH-23390 decreased
circling when injected intrastriatally and increased the number of rotations when
injected intranigrally (pars reticulata (SNr)). These data reveal that
STN-HFS-induced contralateral circling is differentially modulated by D1 and D2
receptors. While D2 receptor-mediated effects involve the dorso-/ventrolateral
striatum and the SNr, D1 receptors probably exert their actions via brain areas
outside the striatum and SNr. These findings suggest the nigrostriatal DA-system
to be specifically involved in the mediation of STN-HFS-induced motor effects.
DOI: 10.1016/j.neuropharm.2004.01.007
PMID: 15081794 [Indexed for MEDLINE]