Buspirone, a serotonergic 5-HT1A agonist, is active in cerebellar ataxia. A new fact in favor of the serotonergic theory of ataxia.
We have previously proposed a serotonergic hypothesis for cerebellar ataxia and mentioned that the levorotatory form of 5-hydroxytryptophan, a serotonin precursor, is partially active in subtypes of cerebellar ataxia, including cerebellar cortical atrophy (CCA). It has been demonstrated that 5-HT1A serotonergic receptors play an important role in the control of Purkinje cells discharges and in the inhibition of the release of glutamate by cerebellar glutamatergic terminals. To test further the serotonergic hypothesis of cerebellar ataxia, we administered buspirone, a 5-HT1A agonist usable in human medicine, in a randomized double blind drug placebo trial for 4 months. Nineteen patients with CCA were included; nine patients were given placebo and 10 Buspirone, at the mean dose of 0.69 mg/kg. The evaluation of ataxia was based on a static and a kinetic ataxia scale, fully quantitative measures and the evaluation of the sway path and area at posturography. At 4 months, a significant effect of buspirone was observed for drug induced gains of the kinetic score, two items of the static score, and the maximum duration of standing upright with feet together. These results indicate that a novel chemical therapeutic approach is possible for cerebellar ataxia; moreover, they support the existence of a link between cerebellar ataxia and disturbances of the serotonergic cerebellar system, especially a serotonergic deficit.
Trouillas
P
P
Ataxia Research Center, Hôpital Neurologique, Claude Bernard University, Lyon, France.
Xie
J
J
Adeleine
P
P
D001007:Anxiety; D001284:Atrophy; D002065:Buspirone / Q000627:therapeutic use*; D002524:Cerebellar Ataxia / Q000188:drug therapy* / Q000503:physiopathology; D002525:Cerebellar Cortex / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D002065:Buspirone