The benzodiazepine agonist diazepam inhibits basal and secretagogue-stimulated prolactin release in vitro.

Benzodiazepines reduce basal and stimulated rat prolactin (PRL) serum levels in vivo. We investigated whether the inhibition of PRL secretion by the benzodiazepine receptor agonist, diazepam, occurs directly at the pituitary. At nanomolar concentrations diazepam did not affect PRL secretion, whereas at micromolar concentrations, diazepam dose-dependently inhibited basal and secretagogue-stimulated PRL release from hemipituitary glands and from primary cultures of rat anterior pituitary cells. The inhibitory effect of the highest concentration of diazepam (100 microM) was abolished when the pituitary tissue was incubated with the benzodiazepine receptor antagonist Ro 15-1788. Although nanomolar concentrations of diazepam alone did not affect PRL release, they did enhance the PRL inhibitory effect of muscimol, a gamma-amino butyric acid (GABA) receptor agonist. Neither diazepam nor muscimol affected cellular adenosine 3',5'-monophosphate (cAMP) content. Since these effects do not appear to occur through an inhibition of the cAMP generating system, diazepam may inhibit PRL release via a cAMP-independent pathway. We suggest that diazepam inhibits PRL secretion either by enhancing the GABAergic inhibition of PRL release, or by inhibiting, at micromolar concentrations, a benzodiazepine-sensitive Ca2+-calmodulin dependent protein kinase.