NMDA receptor antagonists block stress-induced prolactin release in female rats at estrus.
In order to evaluate the role of glutamate in prolactin secretion, we examined the effects of N-methyl-D,L-aspartic acid (NMDA) receptor antagonists on serum prolactin levels at both resting and restraint-stress conditions in female rats at estrus. NMDA increased basal serum prolactin levels. Administration of the selective NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) (5 and 10 mg/kg i.p.), to rats under resting conditions enhanced basal prolactin levels. A low dose of CGS 19755 (3 mg/kg) was unable to modify the hormone serum level. Under stress conditions the pretreatment with CGS 19755 (3 and 5 mg/kg) prevented the increase in serum prolactin levels. This effect was reversed by NMDA (60 mg/kg s.c.). The NMDA receptor antagonist (5 mg/kg) decreased the median eminence concentration of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), without modifying dopamine content. To examine the probable link between serotonin (5-HT) and glutamate in prolactin release, the 5-HT2A/5-HT2C receptor antagonist, ritanserin, was used. Under resting conditions, a dose of 5 mg/kg s.c. blocked the NMDA-induced prolactin release. In rats submitted to restraint, ritanserin decreased the prolactin response and NMDA was unable to correct the stress serum prolactin levels. The 5-HT1A receptor agonist, 8-hidroxypropyl-amino tetralin (8-OH-DPAT) (3 mg/kg s.c.), increased basal serum prolactin levels and restored serum prolactin in stressed animals pretreated with CGS 19755 (5 mg/kg). The present data strongly suggest that the glutamatergic system participates in the regulation of prolactin secretion. A stimulation tone seems to be exerted via the tuberoinfundibular dopaminergic system, and the prolactin release evoked by restraint apparently involves glutamate/NMDA receptors linked to a serotoninergic pathway.
Laboratorio de Investigaciones Cerebrales, LINCE-CONICET, and Facultad de Ciencias Médicas, UN, Cuyo, Mendoza, Argentina. lince@lanet.losandes.com.ar
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004971:Estrus / Q000097:blood / Q000378:metabolism*; D005260:Female; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D016713:Ritanserin; D012701:Serotonin; D011388:Prolactin; D004298:Dopamine