Effect of glutamate receptor antagonists on suckling-induced prolactin release in rats

The aim of the present study was to investigate the role of endogenous excitatory amino acid receptors in suckling-induced prolactin (PRL) elevation. Glutamate is known to be the dominant excitatory neurotransmitter and may act simultaneously on different glutamatergic receptor subtypes. MK-801 (dizocilpine) is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA), while GyKl 52466 is an antagonist of the R,S-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor subtypes. Using the combination of the two receptorsubtype antagonists, we tested the hypothesis that parallel blockade of more than one subtype is more effective. Low-dose MK-801 (0.033 mg/kg) had no effect on suckling-induced PRL elevation after 4 h of separation. When injected alone, 10 mg/kg of GyKl 52466 was also ineffective, but in combination with low-dose MK-801 it efficiently diminished the suckling-induced PRL elevation while lactation proceeded. The same dose of GyKl 52466 combined with 0.2 mg/kg of MK-801 (a combination that in other studies was able to block the foot-shock-induced PRL elevation) was more effective. Simultaneous blockade of the two ionotropic glutamate receptors with 0.2 mg/kg of MK-801 and 10 mg/kg of GyKl 52466 caused a decline in plasma PRL concentration of continuously suckling mothers. We conclude that the endogenous glutamatergic system has an important role in suckling-induced PRL elevation and in the maintenance of constantly high PRL levels in lactating mothers. Furthermore, the NMDA and AMPA/kainate receptor subtypes can interact with each other in this process.