A single dose of the serotonin neurotransmission agonist paroxetine enhances motor output: double-blind, placebo-controlled, fMRI study in healthy subjects.
Since serotonin (5-HT) stimulates motor function, pharmacological potentiation of 5-HT neurotransmission may improve motor function in healthy subjects and, possibly, recovery in post-stroke patients. Indeed, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increased activation in executive motor areas of healthy subjects as fenozolone, a releaser of monoamines (including noradrenaline, dopamine, and serotonin) from intracellular stores. This study is intended to test the hypothesis that paroxetine can likewise modulate brain motor activity in a dose-dependent manner in healthy subjects. In a double-blind counterbalanced study, six subjects underwent functional MRI examinations on three sessions 1 week apart (E1, E2, and E3) at the time of peak plasma concentrations (5 h after drug intake, i.e., either 20 or 60 mg of paroxetine or placebo) with a complex sequential opposition task. Rest and activation alternated in a block design. During activation, subjects performed, with the right hand, a 1-Hz-paced task that alternated two fist closings with a sequential opposition task. Paroxetine elicited effects similar to those reported for fluoxetine; notable changes were hyperactivation in the contralateral S1/M1, and posterior SMA and widespread hypoactivation of basal ganglia and cerebellum. There was an inverse correlation between dose and effect: significantly greater effects were observed with the 20-mg dose compared with 60 mg. Paroxetine dose-dependently modulates activation of the entire motor pathway in a way that favors motor output. Thus, a single dose of the SSRI paroxetine reorganized motor processing.
Loubinoux
Isabelle
I
INSERM U455, Pavillon Riser, Hôpital Purpan, 31059 Toulouse, France. isabelle.loubinoux@purpan.inserm.fr
Pariente
Jérémie
J
Boulanouar
Kader
K
Carel
Christophe
C
Manelfe
Claude
C
Rascol
Olivier
O
Celsis
Pierre
P
Chollet
François
F
D000328:Adult; D001288:Attention / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009044:Motor Cortex / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects*; D017374:Paroxetine / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013003:Somatosensory Cortex / Q000187:drug effects*
D017366:Serotonin Receptor Agonists; D017374:Paroxetine