Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks

Fluoxetine inhibits the reuptake of serotonin, and dextroamphetamine enhanc es presynaptic release of monoamines. Although the excitatory effect of bot h noradrenaline and dopamine on motor behavior generally is accepted, the r ole of serotonin on motor output is under debate. In the current investigat ion, the authors evidenced a putative role of monoamines and, more specific ally, of serotonin in the regulation of cerebral motor activity in healthy subjects. The effects on cerebral motor activity of a single dose of fluoxe tine (20 mg), an inhibitor of serotonin reuptake, and fenozolone (20 mg/50 kg), an amphetamine-like drug, were assessed by functional magnetic resonan ce imaging. Subjects performed sensorimotor tasks with the right hand. Func tional magnetic resonance imaging studies were performed in two sessions on two different days. The first session, with two scan experiments separated by 5 hours without any drug administration, served as time-effect control. A second, similar session but with drug administration after the first sca n assessed drug effects. A large increase in evoked signal intensity occurr ed in the ipsilateral cerebellum, and a parallel, large reduction occurred in primary and secondary motor cortices (P < 10(-3)). These results are con sistent with the known effects of habituation. Both drugs elicited comparab le effects, that is, a more focused activation in the contralateral sensori motor area, a greater involvement of posterior supplementary motor area, an d a widespread decrease of bilateral cerebellar activation (P < 10(-3)). Th e authors demonstrated for the first time that cerebral motor activity can be modulated by a single dose of fluoxetine or fenozolone in healthy subjec ts. Drug effects demonstrated a direct or indirect involvement of monoamine s and serotonin in the facilitation of cerebral motor activity.