‘Peripheral’ Benzodiazepine Receptor Ligands Stimulate Prolactin Release in the Rat

High concentrations of ‘peripheral’ benzodiazepine binding sites have been described in the pituitary gland and in several other endocrine glands, such as the adrenal glands and the testes. The role played by these receptors on the regulation of the endocrine system is largely unknown. In this study, we report the effects of two ligands of the ‘peripheral’ benzodiazepine receptor, Ro5–4864 and PK 11195, on prolactin (PRL) release in the adult male rat. Ro5‐4864 stimulated PRL release with half maximal and maximal stimulatory doses of about 0.6 and 1.2 mg/kg, respectively. Pretreatment with the ‘peripheral’ benzodiazepine receptor antagonist PK 11195 did not have any effect on Ro5‐4864‐induced PRL release. Accordingly, PK 11195, given alone, stimulated PRL release in a dose‐dependent fashion. To examine whether the stimulatory effect of Ro5‐4864 and PK 11195 on PRL release was due to a direct effect of these compounds at the pituitary gland, we used primary cultures of anterior pituicytes. Neither Ro5‐4864 nor PK 11195 had an effect on basal PRL release nor were these agents capable of modulating thyrotropin‐releasing hormone‐stimulated or dopamine‐inhibited PRL release. These findings suggest that administration of agents that interact with the ‘peripheral’ benzodiazepine binding receptor cause PRL release without directly stimulating the pituitary gland. We speculate that Ro5–4864 and PK 11195 increase plasma PRL levels by modulating brain release of neurotransmitters and/or neuropeptides involved in the regulation of PRL release. Copyright