Brain Research, 116 (1976) 23-33 23 © ElsevierScientificPublishing Company,Amsterdam- Printed in The Netherlands RETROGRADE AMNESIA AFTER ELECTRICAL STIMULATION OF THE SUBSTANTIA NIGRA: MEDIATION BY THE DOPAMINERGIC NIGRO- NEOSTRIATAL BUNDLE H. C. F1BIGERand A. G. PHILLIPS Division of Neurological Sciences, Departments of Psychiatry and Psychology, University of British Columbia, Vancouver, B.C. (Canada) V6T 114:5 (Accepted March 8th, 1976) SUMMARY Stimulation of the zona compacta of the substantia nigra (SNC) has been reported to impair the long-term retention of a passive avoidance step-down task. In the present experiments it was observed that previous ipsilateral lesions of the dopaminergic nigro-neostriatal bundle (NSB) with 6-hydroxydopamine blocked the stimulation-induced memory deficit. Unilateral or bilateral lesions of the dopaminer- gic NSB did not by themselves disrupt acquisition or retention of the passive avoid- ance task. In addition, the memory deficit observed after electrical stimulation of the caudate-putamen was not reduced by ipsilateral NSB lesions. These results indicate that the retention deficit produced by stimulation of the SNC was mediated by the dopaminergic NSB. However, in view of the fact that lesions of this projection did not affect acquisition or retention of the step-down task, it is suggested that this system is not critically involved in learning and memory. Rather, it is hypothesized that stimulation of the SNC results in an excess release of dopamine in the caudate- putamen which interferes with neurochemical and neurophysiological events in this structure which are important substrates for long-term memory. INTRODUCTION The neurochemical and neurophysiological substrates of learning and memory have been the subject of extensive experimental analysis during the past 20 years. One approach to this problem has been to disrupt normal neurophysiological events which may be critical in learning and memory by electrical stimulation of discrete anatomical sites. In one such study, Routtenberg and Holzman27 demonstrated that unilateral electrical stimulation of the zona compacta of the substantia nigra (SNC) during or immediately after the acquisition of a passive avoidance step-down task