Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors. Life Sci
Institute of Pharmacology, Medical School, University of Turin, Italy.Life Sciences (Impact Factor: 2.7). 02/1988; 42(24):2457-65. DOI: 10.1016/0024-3205(88)90344-X
We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modifications induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17 beta-estradiol (E2) at both low (0.1 micrograms/kg) and high (20 micrograms/kg) doses confirmed its ability to increase the number of striatal 3H-Spiperone (3H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E2, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophyseal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusion: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of its antiestrogenic activity.
- Pharmacological Research 01/1989; 21(1):93-4. DOI:10.1016/1043-6618(89)90129-1 · 4.41 Impact Factor
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ABSTRACT: Recent evidence has shown that sexual steroids are able to modify the activity of the dopaminergic nigrostriatal pathway. Most of this evidence has been obtained from the individual effects of these hormones, but there is less information about possible interrelationships between both. In order to further explore this question, ovariectomized adult rats were submitted to estradiol (E2) or vehicle injections during 3 days and, at the third day, were also submitted to a single injection of progesterone (P) or vehicle at 4, 10, 24 and 32 h before decapitation. Additionally, the effect of injections of 2-hydroxyestradiol (2OH-E2), which has been involved as local mediator in the effects of E2, was also examined. The two striata of each animal were removed and used for determination of number and affinity of dopamine D2-receptors, using [3H]spiroperidol as ligand. Administration of E2 produced a significant reduction in the number of striatal dopaminergic receptors 10 h after the last steroid injection, which was followed by an increase at 24 h. Administration of P briefly decreased the number of dopaminergic receptors at 4 h after the steroid injection. This effect was not observed in animals pretreated with E2, in which administration of P produced an apparent increase 24 h after the steroid treatment. On the other hand, the 2-hydroxylated derivative of E2 does not seem to mediate in the stimulatory action of this estrogen, since it was unable to increase the number of dopaminergic receptors by itself or priming the action of P. The affinity of dopaminergic receptors for [3H]spiroperidol was not significantly altered after all the steroid treatments.(ABSTRACT TRUNCATED AT 250 WORDS)Brain Research 02/1989; 476(2):388-95. DOI:10.1016/0006-8993(89)91266-3 · 2.84 Impact Factor
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ABSTRACT: The ability of tamoxifen, an antiestrogen agent, to antagonise the striatal dopamine receptor hyperactivity induced in rats by chronic treatment with 17β-estradiol and 2-hydroxyestradiol or with two receptor blockers (haloperidol and sulpiride) was compared. It was found that tamoxifen antagonised both the increase in [3H]spiperone binding sites and the stereotyped behaviour induced by apomorphine in animals treated with the two steroids but had no effect in animals receiving the two dopamine blockers. These results run counter to the view that introduction of a catechol group in a steroid molecule is of decisive importance in the induction of striatal dopamine receptor hypersensitivity.European Journal of Pharmacology 08/1989; 166(2-166):149-156. DOI:10.1016/0014-2999(89)90054-X · 2.53 Impact Factor
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