Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats.
Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells. Amantadine, given in the subcutaneous doses of 50, 5 and 0.5 mg/kg of body weight attenuated the stimulatory effect of stilboestrol on serum prolactin concentration in a dose-dependent fashion. On the other hand, the incorporation of 3H-thymidine into DNA pituitary cells in all the groups of amantadine-treated rats was only slightly suppressed. In an additional experiment, Scatchard analyses were performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture prepared from the pituitaries of 6-week diethylstilboestrol-treated rats. It has been found that amantadine injected in the dose of 5 mg/kg of body weight for 14 days induced a twofold decrease in the density of dopamine D2 binding sites (36.6 +/- 9.4 vs. 70.3 +/- 3.4 fmol/10(6) cells; p less than 0.02), while the apparent affinity of the receptors was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Krawczyk
Z
Z
Institute of Endocrinology, University School of Medicine, Lodz, Poland.
Lyson
K
K
Stawowy
A
A
Pisarek
H
H
Stepien
H
H
D000547:Amantadine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism*
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D004054:Diethylstilbestrol; D011388:Prolactin; D004247:DNA; D000547:Amantadine