THE EFFECT OF NIGRAL IMPLANTATION ON SENSITIZATION TO DOPAMINE AGONISTS IN 6-HYDROXYDOPAMINE-LESIONED RATS

The implantation of fetal nigral tissue into the striatum of patients with Parkinson's disease is a promising approach to treatment which ma y produce clinical benefit partly by influencing drug responsiveness. The purpose of the present study was to determine the pharmacological mechanisms which drug response changes by measuring to what extent sen sitization produced by repeated apomorphine treatment was attenuated b y tissue implantation in rats with nigrostriatal lesions. Prior to imp lantation of nigral cell suspensions, the daily administration of apom orphine to rats with unilateral 6-hydroxydopamine lesions produced a p rogressive increase in the magnitude and duration of rotational behavi our. After implantation, apomorphine-induced rotational effects were r educed to levels observed upon the initial exposure to drug and did no t increase following repeated treatment. Attenuated responses to selec tive D-1 and D-2 agonists were also observed after implantation. In ve hicle-implanted rats, the initial response to apomorphine was attenuat ed but then increased following repeated apomorphine administration. N o attenuation in responses to selective D-1 and D-2 agonists was obser ved in this group. Cell suspensions prepared from fresh and cyropreser ved tissue produced similar behavioural effects, even though the volum e of transplanted striatum exhibiting tyrosine hydroxylase activity wa s greater with fresh tissue. The duration of rotational behaviour indu ced by apomorphine was not affected by cell implantation. These findin gs suggest that the expression of sensitization in an animal model of parkinsonism may disappear after a period without drug treatment. Impl antation of nigral tissue may produce beneficial results in parkinsoni sm by limiting the development of dopamine agonist-induced sensitizati on. (C) 1997 IBRO. Published by Elsevier Science Ltd.