Chronic haloperidol affects striatal D2-dopamine receptor reappearance after irreversible receptor blockade

Brain Res. 1987 Dec 1;435(1-2):147-52. doi: 10.1016/0006-8993(87)91595-2.


The time course of recovery of [3H]spiperone binding in the rat striatum after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was studied in chronically haloperidol-treated rats (0.5 mg/kg, i.p., twice a day for two weeks). Chronic neuroleptic treatment significantly enhanced the [3H]spiperone Bmax value. EEDQ (6.0 mg/kg, i.p.) produced a similar profound decrease of [3H]spiperone binding site density in both saline- and haloperidol-treated rats. However, the receptor degradation rate constant in the haloperidol-treated animals (k = 0.0051 h-1) and the receptor production rate (r = 1.6 fmol/mg prot/h) were lower than in the saline-treated rats (k = 0.0074 h-1; r = 1.8 fmol/mg prot/h). These results are different from what is found in 6-OH-dopamine lesioned rats. D2-receptor recovery after EEDQ administration is enhanced in chronically (4-5 weeks) denervated striatum (Brain Research, 329 (1985) 225-231) while the degradation rate constant is unchanged. Thus, the present results indicate that chronic haloperidol treatment reduces both the degradation and production rates of striatal D2-receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism*
  • Haloperidol / pharmacology*
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / biosynthesis
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2
  • Spiperone / metabolism


  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Spiperone
  • Haloperidol