Regulation of prolactin secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in male rats

The secretion of PRL is controlled by different hypothalamic signals. Depen ding on the experimental model, PRL secretion increases or decreases after activation of N-methyl-D-aspartic acid and kainate receptors. Recently we h ave described that activation of alpha -amino-3-hydroxy-5-methylisoxazole-4 -propionic acid (AMPA) receptors inhibits PRL secretion in prepubertal male rats. The aim of present study was to examine (1) the physiological releva nce of this finding, (2) the possible age-related changes observed after ac tivation or blockade of AMPA receptors, (3) the specificity of the AMPA eff ect, (4) the hypothalamic and/or pituitary localization of AMPA action, and (5) the mechanism(s) of action of AMPA agonists. In a first set of experiments, neonatal males (5 and 10 days old) and prepu bertal (23 days old) male rats were injected with AMPA (1, 2 5 or 5 mg/kg) or the antagonist of AMPA receptors 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-be nzo (f) quinoxaline-7-sulfonamide (NBQX; 0.25 or 0.50 mg/kg). Serum PRL con centrations decreased significantly 15 and 30 min after i.p. administration of AMPA in prepubertal male rats, while the inhibitory effect of AMPA was not observed in 5- and 10-day-old males. The effect of AMPA was abolished b y NBQX but not by MK-801 (a selective antagonist of NMDA receptors). NBQX a lone (0.25 or 0.50 mg/kg) had no effect on PRL release. In vitro, AMPA slig htly stimulated PRL secretion by hemipituitaries from prepubertal males, su ggesting that the hypothalamus is likely the site of action for the reporte d inhibitory action of AMPA on PRL release. In this sense, the blockade of AMPA effects in animals pretreated with domperidone ja dopaminergic antagon ist) or a-methyl-p-tyrosine tan inhibitor of dopamine synthesis) suggests t hat an increase in the release of hypothalamic dopamine is probably the mec hanism involved in the effect of AMPA. In a second set of experiments, the effects of AMPA (2 5 mg/kg i.p.) and NBQX (0.5 mg/kg i.p. and 30 Or 10 nmol i.c.v.) were tested in freely moving adult male rats sampled during period s of 2, 3 or 6 h. In contrast with data obtained in prepubertal rats, neither AMPA nor NBQX a ffected PRL secretion. In conclusion, these data indicate that activation o f AMPA receptors inhibits PRL secretion in prepubertal male rats. This effe ct probably involves the release of dopamine from the hypothalamus and disa ppears in adulthood.