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

Abstract

The secretion of PRL is controlled by different hypothalamic signals. Depending on the experimental model, PRL secretion increases or decreases after activation of N-methyl--aspartic acid and kainate receptors. Recently we have described that activation of -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 relevance of this finding, (2) the possible age-related changes observed after activation or blockade of AMPA receptors, (3) the specificity of the AMPA effect, (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 prepubertal (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-benzo (f) quinoxaline-7-sulfonamide (NBQX; 0·25 or 0·50 mg/kg). Serum PRL concentrations 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 by NBQX but not by MK-801 (a selective antagonist of NMDA receptors). NBQX alone (0·25 or 0·50 mg/kg) had no effect on PRL release. In vitro, AMPA slightly stimulated PRL secretion by hemipituitaries from prepubertal males, suggesting that the hypothalamus is likely the site of action for the reported inhibitory action of AMPA on PRL release. In this sense, the blockade of AMPA effects in animals pretreated with domperidone (a dopaminergic antagonist) or -methyl-p-tyrosine (an inhibitor of dopamine synthesis) suggests that an increase in the release of hypothalamic dopamine is probably the mechanism 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 20 or 40 nmol i.c.v.) were tested in freely moving adult male rats sampled during periods of 2, 3 or 6 h. In contrast with data obtained in prepubertal rats, neither AMPA nor NBQX affected PRL secretion.In conclusion, these data indicate that activation of AMPA receptors inhibits PRL secretion in prepubertal male rats. This effect probably involves the release of dopamine from the hypothalamus and disappears in adulthood.

Ghrelin Inhibits Prolactin Secretion in Prepubertal Rats

“…The available data indicate that ghrelin action is exerted via mechanisms different from those used by EAAs, since: (a) the inhibitory action of NMDA, KA and AMPA upon PRL secretion appeared to be dependent on an increase in DA release [19, 20, 21, 22, 23, 24, 25, 31], and (b) ghrelin significantly inhibited PRL-stimulated secretion by elevation of the serotoninergic tone (with fluoxetine + 5-HTP), whereas AMPA was ineffective in this experimental model [32]. Despite the possibility of different mechanisms of action for the effects of ghrelin and EAAs, in our experiments, the effects of ghrelin and the agonists of ionotropic EAA receptors NMDA and AMPA were not additive, which suggests that each compound, at the doses used, maximally inhibited the PRL secretion and no further decreases can be induced by simultaneous administration of agonists of ghrelin and ionotropic EAA receptors.…”

“…Experiment 6: We have previously described that in prepubertal rats, activation of NMDA, KA or AMPA receptors decreases PRL secretion [21, 22, 23, 24, 25, 26, 27, 32]. To analyze the possible interactions between the inhibitory effects of EAAs (through NMDA and AMPA receptors) and ghrelin on PRL secretion, 23-day-old male rats were i.p.…”

“…Dopamine (DA) is the major central inhibitory signal [20]. Likewise, excitatory amino acids (EAAs), acting through ionotropic NMDA, KA and AMPA receptors, inhibit PRL release in prepubertal rats [21, 22, 23, 24, 25, 26, 27]. In contrast, serotonin (5-HT), vasoactive intestinal peptide, thyrotropin-releasing hormone and other neuropeptides increase PRL release [23, 27, 28, 29, 30].…”

5-HT1 and 5-HT2 receptor activation reduces N-methyl-D-aspartate (NMDA)-stimulated LH secretion in prepubertal male and female rats

“…injected 45 min before administration of AMPA. The protocol for Fx plus 5-HTP administration was selected on the basis of previous studies showing an increase in prolactin (PRL) secretion (11,22).…”

“…Activation of N-methyl-D-aspartate (NMDA) and Kainate (KA) receptors increases luteinizing hormone (LH) secretion (8 -10), whereas (^)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors probably do not participate in the regulation of LHRH/LH secretion (11,12).…”