Norepinephrine manipulation and postoperative practice influence recovery of locomotor placing following cortical lesions in the rat

Abstract

The NE neurotransmitter system has been of interest for its role in recovery of function following SMC lesions as well as its role in sensorimotor learning. Drugs that enhance NE activity have been shown to facilitate recovery of locomotor placing following SMC lesions in the rat while drugs that deplete NE retard recovery (Irish, 1994; Irish, Davis, & Barth, 1995). It has been proposed that drugs that enhance NE activity facilitate recovery by activating distant areas depressed following brain damage (Feeney & Sutton, 1988). Similar to the effects of NE-acting drugs on recovery, manipulations of NE also influence the rate of recovery. Therefore, an alternative explanation of the NE effect on recovery might be that NE-acting drugs affect recovery by influencing sensorimotor learning as the rat learns an alternate behavioral strategy to compensate for the lost function. The present study hoped to elucidate the mechanisms of recovery on the foot-fault test and the beam-walking task by manipulating, postoperative practice and NE levels. Following surgery subjects were divided into either practice or no-practice groups. Postoperative testing began for the practice groups on day 2 and for the no practice groups on day 14. Subjects were given injections of saline, yohimbine, or clonidine every other day beginning on postoperative day 2. It was hypothesized that if NE-acting drugs influence recovery merely through a relief of diaschisis then pharmacological manipulations would influence recovery regardless of postoperative practice. On the other hand, if NE-acting drugs influence recovery through enhancement of learning strategies then no drug effect would be observed until it was given in conjunction with postoperative practice. The findings were that postoperative practice had the strongest influence on recovery of slips and misses on the foot-fault test and recovery of beam-walking ability. NE-acting drugs only influenced recovery of foot slips and this influence appears to be independent of postoperative practice. Therefore, both a release from diaschisis and sensorimotor learning may be acting in the recovery process. NE-acting drugs may affect diaschisis while practice affects sensorimotor learning.