COMPARATIVE EFFECTS OF FLUOXETINE, AMITRIPTYLINE AND SEROTONIN ON FUNCTIONAL MOTOR RECOVERY AFTER SENSORIMOTOR CORTEX INJURY

A recent investigation of the effects of the antidepressants desiprami ne and trazodone on behavioral recovery in brain-injured animals sugge sted that antidepressants, which act to increase noradrenergic activit y in the brain, may facilitate the rate of recovery, whereas those tha t act to increase serotonergic (5-HT) activity may hinder recovery and reinstate deficits in recovered animals. The present study was design ed to evaluate these findings further by assessing the effect of a sin gle intraperitoneal injection of fluoxetine (a relatively pure 5-HT re uptake blocker), amitriptyline (a mixed 5-HT and noradreneregic reupta ke blocker with alpha1-adrenergic receptor blocking activity) or a sin gle intraventricular infusion of 5-HT on recovery of beam-walking abil ity in animals with a unilateral sensorimotor cortex injury. None of t he drugs significantly affected the rate of recovery. Although fluoxet ine was ineffective in reinstating the motor deficit in recovered anim als, amitriptyline reinstated the deficit in a dose-dependent fashion. Infusion of 5-HT resulted in an extremely transient reinstatement of the deficit, which was largely attributable to its short-term sedative properties. These results suggest that 5-HT may be less involved in f unctional recovery than previously thought. They also add further supp ort to previous findings that indicate that drugs which act to antagon ize alpha1-adrenergic activity (e.g., phenoxybenzamine) may interfere with motor recovery after sensorimotor cortex injury. An appreciation of the potential impact of certain antidepressants on functional recov ery in brain-injured patients appears warranted.