Pharmacology Biochemistry & Behavior, Vol. 16, pp. 285-291, 1982. Printedin the U.S.A. Effects of Estrogen on Striatal Dopamine Receptor Function in Male and Female Rats ROBERT E. HRUSKA, LYNN M. LUDMER, KAREN T. PITMAN, MARC DE RYCK AND ELLEN K. SILBERGELD Neurotoxicology Section, NINCDS, N1H, Bldg. 9, Rm. 1E127, Bethesda, MD 20205 Received 5 August 1981 HRUSKA, R. E., L. M. LUDMER, K. T. PITMAN, M. DE RYCK AND E. K. SILBERGELD. Effects of estrogen on striatal dopamine receptor function in male and female rats. PHARMAC. BIOCHEM. BEHAV. 16(2) 285-291, 1982.- The present study compares, biochemically and behaviorally, the effect of estrogen on central dopamine (DA) function in male and female rats. Estrogen has no direct effect in vitro on DA receptors from striatal tissue of male or female rats. In vivo administration of 17/3-estradiol valerate to male or long-term ovariectomized female rats significantly increases the density of the striatal DA receptors by about 20 percent. Behaviorally, normal female rats have more intense stereotypy produced by apomorphine (APO stereotypy), regardless of the phase of their estrous cycle, than normal male rats, while the density of striatal DA receptors is equal. Estrogen administration to male rats increases their APO stereotypy. Normal intact female rats have no changes in APO stereotypy after the administration of estrogen. However, ovariectomy of female rats increases APO stereotypy, and estrogen administration decreases APO stereotypy back to the levels observed in normal intact female rats. In the male rat there is a good correlation between the increased striatal DA receptor density and the increased APO stereotypy, but in the female rat factors other than striatal DA receptor density appear to be important in the regulation of APO stereotypy. Estrogen Dopamine Dopamine receptors Striatum Stereotypy Estrous cycle THERE is now considerable evidence that administration of estrogen to adult rats produces changes in dopamine (DA) function in the striatum, as measured biochemically and be- haviorally. A controversy has developed concerning the direction of the changes. This is complicated by the use of rats of both sexes, use of differeing doses of estrogen and duration of treatment, and use of differing methods of meas- urements. We have found that 6 days after administration of a single high dose of 17fl-estradiol valerate (125 /xg/rat) to adult male rats there is an increase in the density of striatal DA receptors and the intensity of stereotypy produced by in vivo stimulation of these receptors by DA agonists [22,23]. Chiodo et al. [6] have found an increase in stereotypy in adult ovariectomized rats two days after the administration of a single dose of 17/3-estradiol benzoate (10 or 100 p.g/kg). Gordon [19] has found a decrease at one day, followed by an increase at two to seven days, in stereotypy in adult ovariec- tomized rats after three days of treatment with a high dose of 17fl-estradiol benzoate (100 p~g/kg/day). A lower dose of 17fl-estradiol benzoate (10/.tg/kg/day) decreased stereotypy at one day after treatment, and had no significant effects at later times. Other investigators have measured, indirectly, DA func- tion in the striatum [13-16]. They have found that apomor- phine increases and haloperidol decreases the concentration of acetylcholine (ACh) in the striatum. While estrogen ad- ministration alone has no effect on ACh levels, this treat- ment significantly blocks the effect of apomorphine and enhances the effect of haloperidol on ACh levels. Gordon et al. [18] reported that the activity of glutamic acid decar- boxylase (GAD), the synthetic enzyme for y-aminobutydc acid (GABA), is decreased in activity in the substantia nigra by estrogen treatment. The decreased enzyme activity in the substantia nigra was interpreted as an index of the decreased activity of the GABA neuronal cell bodies projecting from the striatum to the nigra, where they may interact with DA cell bodies. The decrease in GAD acitivity was proposed to be compensatory to a decrease in DA efficacy in the striatum. Clinically, elevated levels of estrogen as occur in preg- nancy or during the use of estrogen-containing oral con- traceptives have been associated with chorea [4, I0, 37]. While fairly uncommon, these choreas are generally associ- ated with childhood episodes of rheumatic fever. In both kinds of chorea the termination of pregnancy or the use of the oral contraceptives is followed quickly by the end of the chorea. Choreiform movement disorders are associated with a relative increase in DA neuronal function in the striatum [41]. Therefore, estrogen could increase choreiform move- ments by increasing DA efficacy in the striatum. Also, two 285