Inhibition of Oestradiol-induced Prolactin Release in a Dual-Cannulated Ovariectomized Rat Model by Carmoxirole, a Peripherally Restricted Dopamine Agonist

Centrally acting dopamine agonists (e.g. bromocriptine) and dopamine transport inhibitors (e.g. GBR12909) are known to inhibit oestradiol‐induced prolactin release. The capacity of peripherally restricted compounds to do likewise, however, is unknown. Here, the effects of the peripherally restricted dopamine receptor agonist carmoxirole on oestradiol‐induced prolactin release were investigated. Dual‐cannulated ovariectomized rats were used, so that a robust, reproducible response to exogenous oestrogen could be induced and sequential blood samples were taken with minimal stress. Carmoxirole (15 mg/kg) inhibited oestradiol‐induced prolactin release, similar to bromocriptine and GBR12909. However, carmoxirole also induced a rapid, transient, oestradiol‐independent release of prolactin. These data show that peripherally restricted dopamine receptor agonists are sufficient to inhibit oestradiol‐induced prolactin release. Like centrally acting compounds, they may therefore be expected to affect the incidence of prolactin‐dependent tumours in rat carcinogenesis studies without inducing central‐mediated side effects.