Effect of adding the D-1 agonist CY 208–243 to chronic bromocriptine treatment of MPTP-monkeys: Regional changes of brain dopamine receptors

Abstract

1. 1. Eleven monkeys were administered N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): eight were treated with bromocriptine for one week and then CY 208–243 (four monkeys) or saline (four monkeys) was added to the bromocriptine treatment. 2. 2. Addition of CY 208–243 increased the therapeutic response observed with the ergot alone without inducing dyskinesia. 3. 3. Following MPTP, [ 3H]-SCH 23390 specific binding to D-1 receptors as well as [ 3H]-spiperone and [ 3H]-N-n-propylnorapomorphine specific binding to D-2 receptors increased in posterior striatum compared to control animals, whereas [ 3H]-SKF 38393 binding to D-1 receptors tended to decrease. 4. 4. Dopamine receptor density was unchanged in anterior striatum of untreated MPTP-monkeys. 5. 5. In the posterior striatum, both dopaminergic treatments decreased towards control values [ 3H]-SCH 23390, [ 3H]-spiperone and [ 3H]-N-n-propylnorapomorphine binding whereas they did not significantly change [ 3H]-SKF 38393 specific binding. [ 3H]-SKF 38393 specific binding increased in anterior striatum of bromocriptine-treated MPTP-monkeys, compared to untreated MPTP-animals, and this increase was abolished in animals treated with bromocriptine + CY 208–243. 6. 6. The present study shows that in MPTP-monkeys, treated or not with DA agonists, the D1 and D2 receptor changes are concentrated in the posterior striatum and that denervation appears to cause a shift from the high to the low affinity agonist state of D1 receptors but not for the D2 subtype.