There is biochemical and pharmacological evidence indicating that estrogens are capable of substantially modulating post-synaptic dopamine (DA) receptor sensitivity in experimental animals. Recent electrophysiological data, showing that estrogens significantly attenuate the ability of apomorphine to inhibit the firing activity of type B dopamine neurons in the rat substantia nigra, suggest that these hormones may also induce subsensitivity of DA autoreceptors. In accord with this hypothesis, estrogen-treated rats showed no marked decrease of motility counts when challenged with apomorphine (20-50 micrograms/kg) from 24 to 72 h after the last hormone administration. Similarly, the decrease of dihydroxyphenylacetic acid (DOPAC) levels induced by apomorphine (20 micrograms/kg) in the caudate nucleus, in oil-treated control rats was almost completely counteracted by estrogen treatment. Dopamine agonists, such as 2-alpha-bromocriptine, piribedil, 3 hydroxyphenylpropylpiperidine and n-propylnorapomorphine, failed to induce hypomotility when administered to estrogen-treated rats. These behavioural and biochemical results, along with the electrophysiological data, indicate that estrogen treatment is able to induce hyposensitivity of DA autoreceptors. These results may be relevant to the clinical findings indicating that the activity of dopamine receptor agonists varies in relation to sex or hormonal treatments.
