EFFECTS OF MORPHINE METABOLITES ON MICTURITION IN NORMAL, UNANESTHETIZED RATS

1 By means of continuous cystometry in normal, unanaesthetized rats, t he effects on micturition of intrathecally (i.t.) administered morphin e-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the two main m etabolites of morphine, were studied and compared with those of i.t. m orphine. 2 Both M6G (0.01, 0.1, and 0.5 mug) and M3G (5 mug) were foun d to have significant effects on micturition. Like morphine (0.1, 0.5, and 10 mug), M6G was able to inhibit the micturition reflex, and prod uce urinary retention and dribbling incontinence in a dose-dependent m anner. The potency of M6G for inhibiting micturition was approximately 10 times higher than that of morphine, and the duration of its effect was longer. All effects of M6G could be reversed by naloxone. 3 M3G ( 5 mug) facilitated the micturition reflex, resulting in decreases in b ladder capacity and micturition volume, and an increase in spontaneous contractile activity. Pretreatment with naloxone (10 mug), which by i tself had no effect on micturition, enhanced the facilitatory effects of M3G. In addition, M3G tended to counteract the inhibitory effects o f both morphine and M6G on micturition. M3G (5 mug) also produced an e xcitatory behavioural syndrome. 4 It is concluded that in rats, i.t. M 3G has excitatory effects on micturition and behaviour, probably not m ediated via opioid receptors. I.t M6G has a potent inhibitory effect o n micturition mediated by stimulation of opioid receptors. It may have effects on somatosensory afferent input in lower doses than those req uired for effects on micturition.