Effect of chronic estradiol treatment on brain dopamine receptor reappearance after irreversible blockade: an autoradiographic study. 1992

M Morissette, and D Lévesque, and T Di Paolo
School of Pharmacy, Laval University, Quebec, Canada.

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011804 Quinolines
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D005260 Female Females
D000317 Adrenergic alpha-Antagonists Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. Adrenergic alpha-Receptor Blockaders,alpha-Adrenergic Blocking Agents,alpha-Adrenergic Receptor Blockaders,alpha-Blockers, Adrenergic,Adrenergic alpha-Blockers,alpha-Adrenergic Antagonists,alpha-Adrenergic Blockers,Adrenergic alpha Antagonists,Adrenergic alpha Blockers,Adrenergic alpha Receptor Blockaders,Agents, alpha-Adrenergic Blocking,Antagonists, alpha-Adrenergic,Blockaders, Adrenergic alpha-Receptor,Blockaders, alpha-Adrenergic Receptor,Blockers, alpha-Adrenergic,Blocking Agents, alpha-Adrenergic,Receptor Blockaders, alpha-Adrenergic,alpha Adrenergic Antagonists,alpha Adrenergic Blockers,alpha Adrenergic Blocking Agents,alpha Adrenergic Receptor Blockaders,alpha Blockers, Adrenergic,alpha-Antagonists, Adrenergic,alpha-Receptor Blockaders, Adrenergic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001345 Autoradiography The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed) Radioautography

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