Effect of chronic estradiol treatment on brain dopamine receptor reappearance after irreversible blockade: an autoradiographic study.
Quantitative autoradiography was used to investigate dopamine receptor repopulation kinetics after irreversible dopamine receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The striatum and substantia nigra of two groups of ovariectomized female rats were compared. One group of rats was pretreated with estradiol (10 micrograms, twice daily, for 2 weeks), and another group received the vehicle. Striatal D1 dopamine receptors had larger degradation and production rate constants, compared with D2 receptors. The D2 receptor degradation rate constant increased rostro-caudally in the striatum of vehicle-treated rats, whereas this was not observed for estradiol-treated animals. A trend similar to that for D2 receptors was observed for the D1 receptor degradation rate constant in the striatum of vehicle-treated rats, whereas in estradiol-treated animals this constant decreased rostro-caudally. In the anterior and the middle parts of the striatum D2 receptor recovery parameters were not affected by chronic estradiol treatment, but in the posterior part estradiol-treated rats had lower receptor degradation and production rate constants. In the anterior part of the striatum, chronic estradiol treatment did not affect the recovery parameters of D1 receptors, whereas lowered receptor degradation and production rate constants were observed in the middle and posterior parts. D1 receptor recovery parameters in the substantia nigra were not affected by chronic estradiol treatment. After EEDQ administration to vehicle-treated rats, striatal dopamine levels decreased gradually, to reach a minimum 4 days later, and returned to control values after 7 days. In estradiol-treated rats, however, dopamine levels increased 2 days after EEDQ. Levels of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid increased in the striatum after EEDQ administration in vehicle-treated rats. Even greater increases that lasted longer were observed in estradiol-treated rats after EEDQ. Striatal levels of serotonin and its metabolite 5-hydroxyindoleacetic acid were not significantly affected by EEDQ or estradiol administration. In summary, estradiol decreased striatal D1 and D2 receptor degradation rate constants, with the greatest effect being observed in the caudal part of the striatum. EEDQ dopamine receptor inactivation also revealed an increase of dopamine and its metabolites in the striatum after estradiol treatment.
School of Pharmacy, Laval University, Quebec, Canada.
M
M
Morissette
D
D
Lévesque
T
T
Di Paolo
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018492:Dopamine Antagonists; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D001679:Biogenic Amines; D018492:Dopamine Antagonists; D011804:Quinolines; D011954:Receptors, Dopamine; D004958:Estradiol; C000470:EEDQ