INTERACTIONS BETWEEN NMDA AND AMPA KAINATE RECEPTORS IN THE CONTROL OF MICTURITION IN THE RAT/

In unanesthetized decerebrate rats, GYKI 52466 -4-methyl-7,8-methylene dioxy-5H-2,3-benzodiazepine hydrochloride), an AMPA/kainate receptor a ntagonist, and MK-801 (dizocilpine), an NMDA receptor antagonist, acte d synergistically to depress the micturition reflex. MK-801 (1 mg/kg i .v.) and GYKI 52466 (4 mg/kg i.v.) administered separately had no or o nly a small depressant effect on reflex bladder contractions but marke dly depressed external urethral sphincter activity. However, in MK-801 -treated rats, GYKI 52466 decreased the amplitude, frequency and durat ion of reflex bladder contractions. These results suggest that both AM PA/kainate and NMDA glutamate receptors are important in the micturiti on reflex pathway and that these receptors may be activated in paralle l at some site in the pathway so that excitatory transmission via only one receptor type is sufficient to mediate reflex activation of the b ladder.