Biochemical effects of treatment with oral contraceptive steroids on the dopaminergic system of the rat

Abstract

The effects of acute and chronic administration of a combination of lynestrenol-mestrenol, a widely employed contraceptive medication, on the dopaminergic system of the rat forebrain and striatum were investigated to better understand the biochemical basis of the neurological side-effects of steroid contraceptive drugs (SCDs). Both acute and chronic treatment increased the disappearance rate of striatal dopamine (DA) after synthesis blockade with alpha-methyl-p-tyrosine (alpha-MpT). Moreover, the conversion of 3H-tyrosine (3H-T) into 3H-DA was increased in the forebrain and striatum after chronic administration of this steroid combination. In the same animals, the utilization of tyrosine (T) is increased.

PIP: The effects of acute (4 days) and chronic (30 days) administration of a combination of lynestrenol-mestranol on the dopaminergic system of the rat forebrain and striata were studied. Mature female Sprague-Dawley rats were used. The dosage most often used was a 5: to .3 mg ratio/kg of body weight given orally. The last dose was given 24 hours before sacrifice. IV injection of tritiated-tyrosine was given at a dose of 1 mCi/kg. Animals were sacrificed at 10 and 25 minutes after injection; brains were removed and tissues immediately frozen and kept until assayed. Polyethylene cannulae were implanted into the lateral brain ventricles 72 hours before the injection of the labeled amino and tyrosine, dissolved in Ringer's solution, at a dose of 7 microCi in each ventricle. These animals were sacrificed and the striata kept frozen. Rats received alpha-methyl-p-tyrosine-methyl ester, 200 mg/kg iv. In each group 4 animals were sacrificed before treatments and at 1, 2, and 4 hours after this inhibitor was administered. Both acute and chronic treatments increased the disappearance rate of striated dopamine (DA) after the synthesis blockade with alpha-methyl-p-tyrosine. This effect may have been present in other areas of the brain also. The conversion of tritiated-tyrosine into tritiated-DA was increased in the forebrain and striatum after the chronic administration of the compound. In these animals the utilization of tyrosine was increased.