A Single Injection of d-Amphetamine Facilitates Improvements in Motor Training Following a Focal Cortical Infarct in Squirrel Monkeys

Abstract

Background. There is growing interest in the use of d-amphetamine (d-AMPH) as a pharmacological treatment to supplement rehabilitative therapy following stroke. Based on the success of earlier animal models, several clinical studies have demonstrated beneficial effects of applying physical rehabilitation while stroke patients are under the influence of d-AMPH. To begin to understand the neural mechanisms underlying this promising adjuvant therapy, the authors examined the effects of a single pairing of d-AMPH and rehabilitative training on motor performance after cortical infarct in squirrel monkeys. Methods. Microelectrode stimulation techniques were used to delineate hand movement areas in the primary motor cortex prior to delivering a unilateral infarct to the complete hand representation. Postinfarct recovery was assessed for 3 groups of monkeys: d-AMPH + training, saline + training, and spontaneous recovery (SR). Postinfarct training groups received 14 consecutive days of motor skill training on a reach and retrieval task. A single injection of d-AMPH (0.25 mg/kg) or saline was given only on the 1st day of training (postinfarct day 10). Monkeys in the SR group had only minimal exposure to the training task once per week to monitor recovery. Results. The results show that a single coupling of d-AMPH + training initiated 10 days after cortical infarct facilitated the rate of recovery and improved performance (68% improvement from 1st day of training) beyond the level achieved by the monkeys in the saline + training group (27% improved from 1st day of training). Conclusions. D-AMPH is a potent modulator of behavioral recovery following an ischemic infarct in nonhuman primates.