Inhibition by bromoestrogens of the effects of estradiol on apomorphine-induced climbing behavior.
The chronic administration of estrogens to mice or rats will result in antidopaminergic effects. Apomorphine-induced climbing behavior in mice, the result of direct stimulation of dopamine receptors in the striatal and mesolimbic regions, is a simple animal model for examining these antidopaminergic effects of estrogens. Bromoestrogens, inhibitors of catechol estrogen formation, have been utilized in order to examine the role of estrogen metabolism in dopaminergic antagonism. Mice were pretreated for 3 days with 2-bromoestradiol, 4-bromoestradiol, or 2,4-dibromoestradiol dibenzoates alone or in combination with estradiol benzoate prior to apomorphine administration. The haloestrogens did not alter the climbing-induced responses elicited by apomorphine, whereas estradiol benzoate clearly attentuated the actions of apomorphine. Furthermore, the bromoestradiol dibenzoates were effective in reversing the effects of estradiol benzoate when the two steroids (estradiol benzoate and a bromoestrogen dibenzoate) were administered simultaneously during pretreatment. Thus, the bromoestrogens are able to inhibit the antidopaminergic effects of estradiol exhibited in the apomorphine-induced mouse climbing model.
Fung
Y K
YK
Department of Oral Biology, University of Nebraska Medical Center, College of Dentistry, Lincoln 68583.
Stevens
J M
JM
Palmer
C W
CW
Brueggemeier
R W
RW
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D013257:Steroids, Brominated / Q000494:pharmacology*
D004965:Estrogen Antagonists; D013257:Steroids, Brominated; D004958:Estradiol; D001058:Apomorphine