Recovery of rewarding effectiveness of lateral hypothalamic self-stimulation following radiofrequency lesions.

Abstract

Following lesions that elevate frequency thresholds for medial forebrain bundle self-stimulation, thresholds often rapidly return toward pre-lesion levels. Why the stimulation's rewarding effect recovers has not been well understood. Small radiofrequency lesions were made through the stimulating electrode to explore some of the mechanisms that could underlie the functional recovery. By tracking post-lesion thresholds under different stimulation regimens, results of Experiment 1 indicated that the electrical stimulation itself did not promote the recovery. Experiment 2 studied the reaction of thresholds at bilateral stimulating electrodes following a unilateral lesion to determine whether a dopamine receptor supersensitivity or another distally-occurring compensation might underlie the recovery. Injection of apomorphine (0.5 mg/kg) after thresholds had returned to pre-lesion levels showed that dopamine receptor supersensitivity did not explain the recovery. As recovery took place at lesioned electrodes, thresholds at intact sites did not decrease, indicating that the recovery may not have been due to a post-lesion compensation occurring distal to the lesion site. In Experiment 3, regional post-lesion decreases in tissue resistance indicated that applying a lesion stimulus induced a change that altered resistance and accounted for threshold increases. Experiment 4 extended that investigation by comparing the effects of lesions on thresholds under constant-current and constant-voltage sources of stimulation. Post-lesion threshold increases seen under constant-current stimulation were not evident when voltage levels were not permitted to vary, indicating that when resistance was altered following a lesion, the effectiveness of the stimulation was reduced. Results of Experiment 5 showed that the refractoriness was not altered after a lesion. A sustained increase in local potential summation was noted, indicating that the lesions affected cells close to the tip of the electrode more than those further away in the stimulation field. The post-lesion recovery of thresholds may be due to local changes in ionic concentration or the occurrence of edema in the tissue around the electrode that temporarily reduces resistance before normalizing over time.