Motor-learning impairment by amantadine in healthy volunteers.
NMDA receptor antagonists impair learning and memory in animal models, presumably by inhibiting long-term potentiation in the motor cortex. Human studies are limited and restricted by the paucity of safe NMDA antagonists. Here, we investigated the contribution of glutamatergic neurotransmission to the capacity of acquiring motor-adaptation learning in humans. In a double-blind design, 200 mg of amantadine (a low-affinity NMDA receptor channel blocker) or a matching placebo were given orally to groups of 14 and 13 human healthy young volunteers, respectively. Blood samples were collected 3 h after treatment to assay plasma concentrations, and the subjects were then tested using a motor-adaptation paradigm consisting of an eight-target-pointing task. To rule out drug-related generalized impairments such sedation, tests measuring motor dexterity and attention were also administered pre- and post-treatment. Comparison of the mean performance levels on the motor-adaptation task revealed that subjects in the amantadine group performed at a lower level than those in the placebo group, but this difference did not reach significance. Interestingly, however, despite plasma amantadine concentrations being relatively low, ranging from 2.09 to 4.74 microM (mean=3.3 microM), they nevertheless correlated negatively with motor learning. Furthermore, when the amantadine group was divided into low-performance and high-performance subgroups, subjects in the former subgroup displayed mean amantadine concentrations 36% higher than the latter subgroup, and performed significantly worser than the placebo group. No change in performance was found on the motor-dexterity and attention tests. Altogether, our results lend support to the hypothesis that normal NMDA receptor function is necessary for the acquisition of motor adaptation.
Hadj Tahar
Abdallah
A
Department of Psychology, University of Montreal, Downtown, Montreal, Que, Canada. abdallah.hadj.tahar@umontreal.ca
Blanchet
Pierre J
PJ
Doyon
Julien
J
D000223:Adaptation, Psychological / Q000187:drug effects; D000328:Adult; D000547:Amantadine / Q000009:adverse effects* / Q000097:blood; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*; D013223:Statistics as Topic
D000978:Antiparkinson Agents; D000547:Amantadine