ALTERATION BY URETHANE OF GLUTAMATERGIC CONTROL OF MICTURITION

The i.v. administration of MK-801 (0.001-3 mg/kg), a non-competitive N MDA receptor antagonist, did not alter reflex bladder activity in unan esthetized decerebrate rat recorded during fast infusion (0.21 ml/min) cystometry or under isovolumetric conditions, but did depress reflex bladder contractions in doses between 0.1 and 3 mg/kg i.v. in the uret hane-anesthetized (1.2 g/kg s.c.) intact rat during fast infusion cyst ometry. The ED(50) and the dose to produce maximal inhibition in ureth ane-anesthetized intact rats were 0.25 mg/kg and 3 mg/kg i.v., respect ively. During slow infusion (0.04 ml/min) cystometry, in unanesthetize d decerebrate rats, MK-801 (0.1-1 mg/kg i.v. or 6-60 mu g i.t.) decrea sed by 12-44% the micturition Volume threshold (V-T) but did not chang e the amplitude and duration of the bladder contractions. The administ ration of a larger i.t. dose (60 mu g) of MK-801 produced no further d ecrease in V-T but decreased the amplitude of bladder contractions by 24%. External urethral sphincter electromyogram activity was reduced o r abolished by MK-801 (0.01-3 mg/kg i.v.) in both unanesthetized decer ebrate and urethane-anesthetized intact rats with ED(50) of 0.12 mg/kg and 0.05 mg/kg, respectively. These results indicate that NMDA recept ors play an important role in both facilitatory and inhibitory central neural control of voiding function and that there is a significant in teraction between urethane anesthesia and NMDA glutamatergic transmiss ion. Thus, even though urethane anesthesia has been useful for studyin g the physiological characteristics of the micturition reflex, it seem s inappropriate for analyzing the normal transmitter role of glutamic acid in reflex voiding.