Effects of crus cerebri lesions and repeated amphetamine treatment on the activity of nigral dopaminergic neurons

Previous research suggests that the firing rate of dopamine (DA) neurons in the substantia nigra pars compacta (SNC) may be altered by repeated DA ago nist treatment. Because changes in the frequency of DA activity could refle ct the firing patterns (e.g., bursting) of the neurons sampled, this study examined both the firing rate and pattern of SNC DA neurons after long-term amphetamine (AMPH) treatment (5 mg/kg d-AMPH s.c. twice daily for 6 days). To assess the contribution of postsynaptic feedback from the forebrain, un ilateral electrolytic lesions were made to the crus cerebri (CC), containin g the striatonigral pathway, prior to AMPH treatment. Single-unit activity of presumed SNC DA neurons was recorded in adult male rats under urethane a nesthesia. Spontaneous firing rate was reduced by AMPH treatment, relative to saline vehicle, but was unaffected by CC or sham lesions. Neurons catego rized as bursting had faster rates of activity than nonbursting cells. AMPH treatment reduced the number of bursts seen in intact rats but increased b ursting in lesioned rats. These results suggest that changes in DA firing r ate previously found after chronic AMPH may reflect altered patterns of act ivity. In addition, the effects of long-term AMPH on the firing patterns of DA neurons appear to be mediated by fibers in the CC. Synapse 38:80-86, 20 00. (C) 2000 Wiley-Liss, Inc.