Amphetamine enhanced motor training following cervical contusion injury

In the United States, 55% of reported spinal cord injuries (SCIs) involve the cervical spinal cord. While cervical (C) level injuries can impair both upper and lower extremity function, it is the impaired function of the upper limb(s) that significantly limits the individual's ability to carry out daily tasks. Damage to the spinal cord results in sensory and motor deficits. A spinal contusion causing bruising of the spinal cord is a clinically relevant surgical model. Because rats use their forelimbs actively within their environment and exhibit fine sensorimotor abilities similar to humans, our experimental model is a mild cervical contusion injury in rats. Animals were trained preoperatively on a skilled reaching task and then received a C3/C4 right side dorsolateral contusion injury (175 Kdyne) using the Infinite Horizon impactor. We identified changes in forelimb motor function resulting from the injury and the effects of pairing skilled motor training and amphetamine (AMPH) administration. AMPH may enhance recovery by temporary activation of circuitry involved in descending motor drive and/or enhancement of attention during a period necessary to solidify the effects of motor training. A battery of behavioral tests was used to assess forelimb motor function. Individual treatments (AMPH and motor training) did not lead to beneficial effects over control animals. The combination treatment increased the qualitative components of skilled reaching in the Whishaw single pellet reaching box, suggesting that the two treatments acted synergistically. We then tested whether the beneficial effects of housing animals in an enriched environment (EE) would further benefit forelimb function in animals given the combination of training and AMPH. An EE in which several animals share a larger environment with items, (tubes, ramps, ladders, running wheels, etc.) increases spontaneous motor activity, provides sensory feedback, encourages social interaction and has been reported to improve function. Surprisingly, housing animals in an EE in combination with daily skilled motor training sessions and AMPH administration decreased their success in skilled behavioral tests. These results suggest a possible treatment strategy for improved motor function following a partial SCI that can be directly translated to the clinic.