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

  • Pich E
  • Benfenati F
  • Farabegoli C
 et al. 
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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 Bmaxvalue. 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. © 1987.

Author-supplied keywords

  • Chronic neuroleptic treatment
  • Dopamine D2-receptor
  • Receptor turnover
  • [3H]Spiperone

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  • Emilio Merlo Pich

  • Fabio Benfenati

  • Costanza Farabegoli

  • Emanuel Meller

  • Marie Aronsson

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