Effect of adding the D-1 agonist CY 208-243 to chronic bromocriptine treatment of MPTP-monkeys: regional changes of brain dopamine receptors.
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. Addition of CY 208-243 increased the therapeutic response observed with the ergot alone without inducing dyskinesia. 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. Dopamine receptor density was unchanged in anterior striatum of untreated MPTP-monkeys. 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. 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.
Gagnon
C
C
School of Pharmacy, Laval University, Quebec, Canada.
Gomez-Mancilla
B
B
Markstein
R
R
Bédard
P J
PJ
Di Paolo
T
T
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000633:toxicity*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D015259:Dopamine Agents; D018491:Dopamine Agonists; D007211:Indoles; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C054531:CY 208-243; D001971:Bromocriptine