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      Effect of Amantadine on Prolactin Secretion, Pituitary DNA Synthesis and 3H-Spiperone Binding in Male Estrogen-Treated Rats

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          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 <sup>3</sup>H-thymidine and <sup>3</sup>H-spiperone binding by the anterior pituitary gland of long-term diethylstil-boestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstil-boestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of <sup>3</sup>H-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 <sup>3</sup>H-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 <sup>3</sup>H-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 D<sub>2</sub> binding sites (36.6 ± 9.4 vs. 70.3 ± 3.4 fmol/l0<sup>6</sup> cells; p < 0.02), while the apparent affinity of the receptors was unchanged. It is concluded then that the inhibitory effect of amantadine on pituitary prolactin cell function seems to be related to the modulation of synthesis and release of dopamine from hypothalamic dopaminergic neurons and to the down-regulation of dopaminergic D<sub>2</sub> binding sites within the anterior pituitary gland.

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          Author and article information

          S. Karger AG
          03 April 2008
          : 51
          : 6
          : 632-636
          aInstitute of Endocrinology and b Department of Neurosurgery, University School of Medicine, Lodz, Poland
          125403 Neuroendocrinology 1990;51:632–636
          © 1990 S. Karger AG, Basel

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          Pages: 5
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