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

Prog Neuropsychopharmacol Biol Psychiatry. 1995 Jul;19(4):667-76. doi: 10.1016/0278-5846(95)00110-h.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Neostriatum / metabolism
  • Ovariectomy
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy
  • Parkinson Disease, Secondary / metabolism
  • Phenanthridines / pharmacology*
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D2 / drug effects

Substances

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