Denervation accelerates the reappearance of neostriatal D-2 receptors after irreversible receptor blockade

Brain Res. 1985 Mar 11;329(1-2):225-31. doi: 10.1016/0006-8993(85)90528-1.


The effect of denervation on the turnover of striatal dopaminergic D-2 receptors was examined by determining the rate of receptor reappearance in vivo after administration of the irreversible receptor antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats that received prior unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA). Initial experiments confirmed that EEDQ (10 mg/kg i.p.) induces a severe, prolonged blockade of D-2 receptors. Recovery of [3H]spiroperidol binding occurred at a rate of approximately 9% of control binding per day. 6-OHDA injection into the ascending dopaminergic projection 3 or 5 days prior to EEDQ administration revealed that denervation had no effect on the rate of D-2 receptor recovery during the first post-operative week. By 4-5 weeks postoperatively, however, denervation enhanced the rate of recovery of [3H]spiroperidol binding. These results are consistent with our finding that, when homogenized tissue preparations are used, steady-state receptor density does not change within the first postoperative week but increases by 3-4 weeks after the injury. Saturation analysis determined that both EEDQ and denervation altered the density of binding sites, whereas neither treatment significantly affected the affinity of the receptor for [3H]spiroperidol. By 4-5 weeks postoperatively, the receptor degradation rate constant in the denervated striatum (0.0054/h) was equal to that in the intact striatum (0.0052/h). Thus, only the receptor reappearance rate was elevated in the denervated striatum (3.8 fmol/mg protein/h) relative to the intact striatum (2.8 fmol/mg protein/h).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Corpus Striatum / analysis*
  • Corpus Striatum / physiology
  • Dopamine / physiology
  • Hydroxydopamines / pharmacology
  • Male
  • Oxidopamine
  • Quinolines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / analysis*
  • Receptors, Dopamine D2
  • Spiperone / metabolism


  • Hydroxydopamines
  • Quinolines
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Spiperone
  • EEDQ
  • Oxidopamine
  • Dopamine