We have investigated the effects of estrogens and prolactin on nigro-striatal dopaminergic function. In this regard, apomorphine-induced hyperactivity has been evaluated in hyperprolactinemic rats. Results obtained suggest the possibility that hyperprolactinemia potentiates nigro-striatal dopaminergic transmission inducing, in chronic, charges in dopamine receptor sensitivity. As a neurochemical parameter of the extrapyramidal motor system, we have investigated the activity of the GABA-synthesizing enzyme glutamate decarboxylase (GAD, EC 4.1.1.15) in corpus striatum and substantia nigra. Hyperprolactinemia induced by anterior pituitary homograft under the kidney capsule or systemic sulpiride injection significantly increases GAD activity. In contrast, estrogen treatment decreases nigral GAD activity even though increases plasma prolactin levels. From a clinical point of view, preliminary data indicating a good therapeutical efficacy of estrogens and progesterone in psychiatric patients are reported.