Exposure to amphetamine after substantia nigra lesion interferes with the process of behavioral recovery

Recovery from unilateral substantia nigra lesion may be indicated by re-emergence of circling in the pre-lesion preferred direction. Following 6-OHDA-induced lesion of the dominant SN, we examined: (a) The effect of the delay from lesioning on amphetamine-induced rotation asymmetry, and (b) The effect of early post-lesion exposure to amphetamine on later rotation asymmetry. d-Amphetamine was initially injected either 7, 14, 21, or 30 days after lesioning. Transient circling in pre-lesion preferred direction (contralateral to lesioned side) was more frequently encountered on days 7 and 30 after lesioning, as compared to days 14 and 21. The contralateral rotation observed on day 7 is attributed to degeneration-induced DA release, whereas contralateral rotation noted on day 30 is believed to reflect the operation of post-lesion compensatory processes within the spared DA neurons. In response to subsequent amphetamine administration 30 days after lesioning, rats with previous exposure to the drug circled ipsilaterally, whereas most rats given amphetamine for the first time in that session rotated contralaterally to the lesion. These findings suggest that post-lesion administration of amphetamine interferes with the process of recovery.