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. 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.

• Authors: C Gagnon, B Gomez-Mancilla, R Markstein, P J Bédard, T Di Paolo
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 19 Issue 4 Pg. 667-76 (Jul 1995) ISSN: 0278-5846 [Print] England
• PMID: 8588064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agents
• Dopamine Agonists
• Indoles
• Phenanthridines
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• CY 208-243
• Bromocriptine

Topics

• Animals
• Autoradiography
• Behavior, Animal (drug effects)
• Brain Chemistry (drug effects)
• Bromocriptine (pharmacology)
• Dopamine Agents (toxicity)
• Dopamine Agonists (pharmacology)
• Female
• Indoles (pharmacology)
• MPTP Poisoning
• Macaca fascicularis
• Neostriatum (drug effects, metabolism)
• Ovariectomy
• Parkinson Disease, Secondary (chemically induced, drug therapy, metabolism)
• Phenanthridines (pharmacology)
• Receptors, Dopamine D1 (agonists)
• Receptors, Dopamine D2 (drug effects)