Permanent haloperidol-induced dopamine receptor up-regulation in the ovariectomized rat

Brain Res Bull. 1991 Apr;26(4):549-52. doi: 10.1016/0361-9230(91)90094-z.

Abstract

One of the confounding problems associated with the study of tardive dyskinesia in rodent models has been the inability to produce a permanent supersensitivity to dopamine (DA) following neuroleptic drugs. We recently observed that ovariectomy (OVX) results in a permanent dopamine receptor (DA-R) up-regulation in the striatum of the rat. This permanent up-regulation of striatal D2 DA-R required three months to fully develop and lasted for at least 12 months post-OVX. In the present study we further characterized this model by examining the development of both apomorphine-induced stereotypy and D2 DA-R density in the striatum of OVX and Sham-operated rats following haloperidol (16 days at 1.0 mg/kg/day, IP). Following the chronic haloperidol treatment, both the OVX and the Sham-operated animals increased both their behavioral responses (stereotypic sniffing) to apomorphine, and the density of striatal D2 DA-R. However, by 30 days posthaloperidol, the Sham animals had reverted to normal behavioral responses to apomorphine and normal levels of striatal DA-R, while both the behavioral responses and the density of D2 DA-R in the OVX animals treated with haloperidol remained up-regulated. These data indicate that 1) the time required to develop this unique animal model of a permanent DA-R up-regulation in the ovariectomized (OVX) rat can be considerably shortened; 2) there is probably a unique neurochemical change induced by haloperidol in the OVX but not in Sham rats that leads to the DA-R up-regulation becoming permanent.

Publication types

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

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Female
  • Haloperidol / pharmacology*
  • Ovariectomy*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2
  • Reference Values
  • Spiperone / pharmacology
  • Stereotyped Behavior / drug effects
  • Time Factors
  • Up-Regulation*

Substances

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