Hypophysectomy induced hypersensitivity to dopamine: antagonism by estrogen.
Hypophysectomized (HYPOX) or sham HYPOX (SHAM) and ovariectomized rats were injected with either estradiol benzoate (EB, 10 microgram/kg/day x 3) or sesame oil (0.25 ml/kg/day x 3). Twenty hours after the last dose of EB or oil all animals were injected with apomorphine and the resulting stereotypy scored. The HYPOX + oil group was more sensitive to the apomorphine than the SHAM + oil group (ED50 = 0.24 and 0.45 mg/kg, respectively). Treatment with EB resulted in a shift to the right of the dose response curves for both the HYPOX and SHAM groups. The ED50 for the HYPOX group was increased to 0.62 mg/kg, while the SHAM group increased to 0.93 mg/kg. The Bmax values for [3H]spiroperidol binding to striatal membranes were not significantly different for the HYPOX + EB, SHAM + EB, or SHAM + oil groups. However, the HYPOX + oil group was significantly increased (54%) at 7 days post-HYPOX. By 28 days post-HYPOX, the Bmax for the HYPOX animals had increased by 94% relative to SHAM animals. The HYPOX induced increase in dopamine sensitivity could be increased by chronic treatment and withdrawal of haloperidol. The haloperidol induced increase in apomorphine induced stereotypy and [3H]spiroperidol binding could be antagonized by EB treatment during the withdrawal phase of the haloperidol treatment. These data indicate that the pituitary has a modulating effect on striatal spiroperidol binding and apomorphine induced stereotypy, but that its presence is not required for estrogen to suppress the efficacy of dopamine or dopamine agonists.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007016:Hypophysectomy; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D004958:Estradiol; D013134:Spiperone; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine