BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons represent the final output cells of the neural network that controls fertility. Dopamine (DA) has been shown to control gonadotropin release in many species. However, the direct membrane effects of DA and the related receptors on GnRH neurons remain poorly understood. The purpose of this study was to investigate the direct actions of DA on GnRH neurons and the related receptors using brain slice electrophysiology. METHODS: Gramicidin-perforated patch clamp recordings were made from the GnRH neurons to examine the direct membrane effects of DA in GnRH-EGFP mut5 mice. RESULTS: DA induced hyperpolarization of the GnRH neurons, which was maintained in the presence of tetrodotoxin (TTX), a Na+ channel blocker, suggesting a direct, rather than indirect, action of DA on GnRH neurons. DA-induced hyperpolarizing effects were blocked by prazosin, an alpah1-adrenergic antagonist, and mimicked by phenylephrine (PE), an alpha1-adrenergic agonist. CONCLUSIONS: These data indicate that DA exerts a direct inhibitory effect on GnRH neurons via the alpha1- adrenergic receptors. These results support the general concept that dopaminergic afference represents a predominantly inhibitory component of the GnRH neuronal network.