Aktuelle Neurologie 2005; 32 - A1
DOI: 10.1055/s-2005-916288

The possible role of Dopamine D3 receptor antagonism on motor activity in rats

PC Baier 1, R Koch 1, D Virley 2, C Trenkwalder 1, 3
  • 1Abt. Klinische Neurophysiologie, Georg-August-Universität Göttingen, Göttingen, Germany
  • 2Neurology & GI CEDD, GlaxoSmithKline, Harlow, UK
  • 3Paracelsus-Elena-Klinik, Kassel, Germany

Although the pathophysiology of RLS still is unclear, the efficacy of levodopa and dopamine D2/D3-receptor agonists on the sensory and motor symptoms of RLS implicate an involvement of the dopaminergic system. We investigated whether symptoms frequently seen in RLS can be observed in rodents, following the chronic (5weeks) daily administration of a selective dopamine D3 (SB-277011–1, SB27) or mixed D2/D3 (sulpiride, SUL) receptor antagonist with polysomnographic and motor activity assessments, performed at baseline and at the end of the treatment phase. Animals treated with SB27 showed an increase in sleep latency and a more fragmented sleep compared with baseline, with increased non-REM episode counts and decreased non-REM episode duration. As a measure for motor activity, the total distance travelled during the12-hour dark phase and entire 12:12-hour L/D assessment period was significantly increased in the SB27 group compared with baseline. We conclude that selective dopamine D3-receptor antagonism, in contrast to combined D2/D3-antagonism, may lead to an increased locomotor activity, a possible correlate to an urge to move, and to sleep disturbance. Although these symptoms mirror those seen in human RLS, further studies are required to validate the role of periodic limb movements during sleep in this pharmacologically induced model.

Study supported by: GlaxoSmithKline Research & Development grant number G2821.