Changes in the nigrostriatal system following microinjection of an unconventional agent

The effect of apomorphine, a direct dopamine receptor agonist, was studied in golden hamsters after unilateral injection of scrapie agent (strain 263K) into the nigrostriatal system. Twenty-five received an injection into the left striatum and 24 into the left substantia nigra. Varying volumes (5, 1 and 0.5 microliterss) and dilutions of the homogenate (10(-2), 10(-3), 10(-4)) were used. The duration of the incubation period (delay of appearance of clinical signs of the disease) was dependent on the dose of the agent used: it varied within a range of 72 +/- 5 days (5 microliter 10(-4) and 123 +/- 8 days (0.5 microliter 10(-4)). Apomorphine-induced circling behavior appeared after an average of 84 +/- 15 days post-injection and this delay was closely related to the dose of agent. The direction of the rotation dependent on the site of injection: most of the animals circled towards the inoculated side after striatal injection and away from it after inoculation in the substantia nigra. In the group of animals inoculated in the substantia nigra with 0.5 X 10(-4) microliters, 6 presented the clinical phase of the disease and showed circling behavior but no clinical signs when they were killed 200 days post-injection. However, neuropathological studies revealed characteristic foci of vacuolation in the brain stem. Apomorphine-induced circling behavior can only be contained by replication of scrapie agent into the nigrostriatal neurons and the subsequent imbalance between the two sides which it reveals. Circling behavior and clinical signs of the disease can be temporally dissociated: low doses of agent slightly extended the circling behavior latency, whereas the incubation period was considerably increased. Circling behavior and neuropathological lesions in nigrostriatal system were not closely related.