Simultaneous blockade of two glutamate receptor subtypes (NMDA and AMPA) results in stressor-specific inhibition of prolactin and corticotropin release

Many neurons express simultaneously two or more isotypes of glutamate recep tors, so that pharmacological modulation of more than one receptor may be n ecessary to reveal the role of glutamate in mediating physiological process es. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic horm one (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-8 01, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rat s were pretreated for 4-5 days and then exposed to stressful stimulation. B asal hormone levels were not affected by the antagonists. In male rats, com bined, but not separate blockade of NMDA and AMPA/kainate subtypes of gluta mate receptors prevented the rise in plasma PRL in response to footshock st ress. In female rats, footshock-induced PRL release was inhibited even by s eparate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobiliz ation or ether stress. Simultaneous blockade of NMDA and AMPA receptor subt ypes resulted in a mild inhibition of immobilization-induced ACTH release w ithout any effect on ACTH response to footshock or ether stress. The data s uggest that involvement of glutamatergic pathways in neuroendocrine respons e during stress is selective for discrete stress stimuli and stress hormone s. In addition a concerted action of glutamate on both NMDA and non-NMDA re ceptor subtypes is involved in the control of PRL release during footshock stress.