Effects of Orchidectomy on Nigro‐Striatal Dopaminergic Function: Behavioral and Physiological Evidence

Abstract

In the present experiments, we examined the effect of castration upon two indices of nigro-striatal dopaminergic function in the male rat. In Experiment I, differences in spontaneous locomotor behavioral activity between intact and castrated male rats were examined. The total distance traveled, horizontal activity and mean revolutions of castrated male rats were significantly greater than that of intact males. No significant differences between intact and castrated males were obtained for vertical activity. In Experiment 11, the spontaneous in vifrodopamine release from the corpus striatum of intact and castrated rats as sampled during the light-phase (1500 h) and dark-phase (2400 h) of the photoperiod was examined. At both time periods, the spontaneous in vifrodopamine release of castrated males was significantly greater than that of intact males. Both intact and castrated males showed statistically significant increases in dopamine release at the 2400 h compared to the 1500 h time period. To examine if testicular hormones were responsible for these castration induced changes in dopamine release, in Experiment Ill we treated castrated male rats with testosterone propionate. Administration of testosterone propionate (0.1 mg/day x 5 days) significantly reduced in vifro dopamine release compared to untreated or castrated male rats receiving vehicle treatment. These results demonstrate that testicular hormones, most likely testosterone, have a markedly suppressive effect upon the nigro-striatal dopaminergic system as evidenced from changes in spontaneous behavioral activity and in vifro dopamine release.Within our laboratory, we have been interested in examining the modulatory effects of gonadal steroid hormones upon the nigrostriatal dopaminergic system of the female rat (1, 2). Our results, as well as those from other laboratories, have demonstrated that the corpus striatum (CS) is an important target site of the CNS for both estrogen and progesterone (3-6). The role of the male gonadal steroid hormone, testosterone, upon the nigro-striatal dopaminergic system has received relatively less attention. Indirect indices of dopaminergic activity as determined with amphetamine-stimulated behavioral measures have indicated that testosterone attenuates the effects of amphetamine on locomotor activity and stereotyped behavior (7-9) and the duration of specific amphetamine-stimulated behaviors in castrated male rats are prolonged compared to those of intact and castrated plus testosterone-treated male rats (10). In addition, castration reduces and testosterone reinstates yawning behavior in male rats (1 l), a behavior, which in part, appears to be under control of the dopaminergic system (12). These results suggest that, similar to that of the female, the nigro-striatal dopaminergic system of the male rat is also subject to the influences of gonadal steroids. More specifically, it would appear that testicular steroids exert a predominantly suppressive effect upon dopaminergic activity in the male rat.In this report...

Castration Induces Parkinson Disease Pathologies in Young Male Mice via Inducible Nitric-oxide Synthase

“…However, in contrast to our finding, some articles have shown either no effect or an increase in markers of nigrostriatal function (e.g. TH-positive neurons in the SN, striatal dopamine content) following castration (29,30). In these cases, older mice or rats were used for castration.…”

Effects of Active Immunization against Gonadotrophin-Releasing Hormone on the Concentrations of Noradrenaline, Dopamine, 5-Hydroxytryptamine and Some of Their Metabolites in the Brain and Sexual Organs of Male Rats

“…The present experiments show that immunization against GnRH produces a small increase in mesolimbic dopamine and striatal homovanillic acid concentration (table 3) while in other series of experiments it was found that testosterone treatment reduced in vitro dopamine release [6], All these experiments agree well with the suggestion that testosterone tends to reduce the activity of mesolimbic or nigro striatal dopaminergic systems.…”

“…It has been known for many years that brain catecholamines have stimulatory effects on male sexual behavior [1][2][3] and that testosterone attenuates some behavioral responses that are me diated by dopamine [4,5], In agreement with these findings, it has been recently shown that testosterone also decreases dopa mine striatal release [6], In addition, brain 5-hydroxytryptamine has been implicated in the regulation of male sexual behavior, as suggested by the finding that synthesis blockade increases rat mounting behavior, an effect that is counteracted by 5-hydroxytryptophan administration [7][8][9].…”

Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats

“…As sex hormones exert unique organizational effects on brain and evolving behavior during adolescence, it is important to study this developmental period. Preclinical studies in mostly adult male rats report that testosterone can both increase (de Souza Silva et al, 2009;Thiblin et al, 1999) and decrease (Beatty et al, 1982;Dluzen and Ramirez, 1989;Forgie and Stewart, 1994;Menniti and Baum, 1981) striatal dopamine activity. Testosterone treatment increased dopamine turnover but not dopamine synthesis in the striatum of adult male rats (Thiblin et al, 1999) and…”