Abstract
Rotational behavior was studied in rats with unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine system, following intrastriatal grafting of pieces of the adrenal medulla or nervus opticus. The rats were placed in rotometers immediately after the operation. No rotational response was seen in animals implanted with nervus opticus. Rats that received one whole adrenal medullary gland, divided into 4 pieces, showed a strong rotational response with a peak after 100 min and a duration of 400 min. Adrenal medulla-induced rotations were dose-dependent: when rats were grafted with 2, 4 or 8 pieces (where 4 pieces equals one whole adrenal medulla) into 2 sites, 2 pieces induced about half the amount of rotation as 4 pieces, while 8 pieces caused a higher total number of rotations with the 100 min peak approximately doubled compared with rats that had received 4 pieces. The coordinates for the implantation site were also important determinants of the rotational behavior: 4 implantation sites were tested and it was shown that the most central site in the caudate caused the highest total amount of rotations. The rotational behavior could be blocked in a dose-dependent manner by the dopamine-receptor antagonists haloperidol and cis-flupenthixol given immediately after grafting. It is concluded that implantation of chromaffin tissue from the adrenal medulla into the unilaterally 6-hydroxydopamine-denervated striatum causes highly reproducible acute rotational responses that vary with the amount and location of the implanted tissue and that can be blocked by neuroleptics. Thus the experiments permit screening of areas within neostriatum that produce different rotational responses to chromaffin implants. This should be useful in designing optimal implantation sites for chronic experiments aimed at permanently counteracting counteracting the symptoms of experimental Parkinson's disease using non-CNS grafts.
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