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 ant agonists on serum prolactin levels at both resting and restraint-stres s conditions in female rats at estrus. NMDA increased basal serum prol actin levels. Administration of the selective NMDA receptor antagonist , cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) (5 an d 10 mg/kg i.p.), to rats under resting conditions enhanced basal prol actin levels. A low dose of CGS 19755 (3 mg/kg) was unable to modify t he hormone serum level. Under stress conditions the pretreatment with CGS 19755 (3 and 5 mg/kg) prevented the increase in serum prolactin le vels. This effect was reversed by NMDA (60 mg/kg s.c.). The NMDA recep tor antagonist (5 mg/kg) decreased the median eminence concentration o f the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), wit hout 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 respon se and NMDA was unable to correct the stress serum prolactin levels. T he 5-HT1A receptor agonist, 8-hidroxypropyl-amino tetralin (8-OH-DPAT) (3 mg/kg s.c.), increased basal serum prolactin levels and restored s erum prolactin in stressed animals pretreated with CGS 19755 (5 mg/kg) . The present data strongly suggest that the glutamatergic system part icipates in the regulation of prolactin secretion. A stimulation tone seems to be exerted via the tuberoinfundibular dopaminergic system, an d the prolactin release evoked by restraint apparently involves glutam ate/NMDA receptors linked to a serotoninergic pathway. (C) 1998 Elsevi er Science B.V. All rights reserved.