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 GyKI 52466 is an antagonist of the R,S-alpha-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 GyKI 52466 was also ineffective, but in combination with low-dose MK-801 it efficiently diminished the sucklinginduced PRL elevation while lactation proceeded. The same dose of GyKI 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 GyKI 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.
Zelena
Dóra
D
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. makara@koki.hu
Makara
Gábor B
GB
Nagy
György M
GM
D000818:Animals; D000833:Animals, Suckling; D001569:Benzodiazepines / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007774:Lactation / Q000187:drug effects* / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D011388:Prolactin