The Effect Of Venlafaxine On Motor Function In Healthy Subject With FMRI Study

Stroke is a common disease characterized with high mortality and high disability. Most stroke patient suffer long-lasting neurological dysfuction sequelae. At present, the hypothesis that the human brain plasticity has close relation to the brain functional rehabilitation has been proven by more and more evidences. Therefore, The brain plasticity after stroke is the first choice to improve the motor deficit.In recent years, studies have shown the benefits of both 5-hydroxytryp-tamine and norepinephrine on modulation of brain plasticity in stroke patients. Venlafaxine, a new generation of antidepressants,as serotonin and norepine-phrine dual analog agents, with less side effects, rapid onset of clinical outcome, is expected to play a more important role in poststoke rehabilitation.ObjectiveIn this study, we observe the effects of venlafaxine on modulation of human motor cortex activation by using fMRI (functional magnetic resonance imaging) associated with behavioral assessment, so as to provide the evidence for further assessing its influence on motor functional reorganization after stroke injury.Methods:1. There wre eight healthy male volunteers recruited in this trial. All of them were right-handed, with normal state of language and cognitive function, with no history of psychiatric disease. They were randomly diveded into group A and group B. Volunteer in group A received 75mg venlafaxine capsule daily in the first week, after a wash-out period of 3 days, then received placebo daily for another week. In contrast, the volunteers in the group B received placebo in the first week, after a wash-out period of 3 days, then received the same dose of venlafaxine capsule for another week.2. Respectively, before the drug was given(prior-intervention stage), and after the placebo (placebo stage) or venlafaxin (venlafaxin stage) was given, the volunteers were asked to execute motor tasks with their both hands, including dynamometer and finger tapping, meanwhile accepted fMRI examin-ation.Result:1. Eight subjects completed the entire experiment. In venlafaxine stage, the venlafaxine serum concentration is 18.60±5.83ng/ml. Whlie it is less than 0.05ng/ml in placebo stage.2. Behavioral results and drug effectsThe number of finger tapping of the right hand was 61.08±6.83 times every 10 sec in venlafaxin stage, compared to 56.71±6.96 times every 10 sec in placebo stage, these is a significant improvement of tapping rate after venlafaxin administration (n=8, F=184.48, P<0.001). The number of finger tapping of the left hand was 51.67±3.09 every 10 sec in venlafaxin stage, compared to 46.12±3.50 every 10 sec in palacebo stage, these is also a significant improvement of tapping rate after venlafaxin administration (n=8,F=57.69, P<0.001).The grip strength of the right hand in venlafaxin stage was 52.54±3.35kg, compared to 51.91±3.29 kg in placebo stage, these is no significant impro-vement of grip strength after venlafaxin administration (n=8, F=2.63, P>0.05) The grip strength of the left hand in venlafaxin stage was 47.60±3.06kg, compared to 47.21±3.12kg in placebo stage, these is also no significant improvement of grip strength after venlafaxin administration (n=8, F=1.60, P>0.05).3. fMRI resultDuring the fMRI examination, both in venlafaxin group or in placebo group, the hands active task has activated the entire movement network, including the contralateral sensory motor cortex. When compared to the activa-tion in placebo stage, the activation of the contralateral S1M1, contralateral PMC and contralateral SMA enhanced in venlafaxin stage. We also observed that the activation of bilateral parietal cortex in venlafaxin stage decreased when campapred to which in placebo stage. Meanwhile, the contralateral S1M1 activ-ation enhancement has a positive correlation to the improvement of the finger tapping rate.ConclusionCompared to the placebo, venlafaxine significantly improved the tapping rate during the finger-tapping test, and induce the significantly enhancement of contralateral S1M1, contralateral PMC and contralateral SMA activation, and the decrease of bilateral parietal cortex activation under fMRI. The finding suggests that venlafaxine can modulate the cortical excitability, improving the movement dexterity and reaction speed. It provides a strong evidence for the study of poststroke rehabilitation.