Permanent haloperidol-induced dopamine receptor up-regulation in the ovariectomized rat.
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.
Fields
J Z
JZ
Research Service (151), Hines V.A. Hospital, IL 60141.
Gordon
J H
JH
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012016:Reference Values; D013134:Spiperone / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D006220:Haloperidol; D001058:Apomorphine