In urethane-anesthetized rats the i.v. administration of the potent short-acting opioid, fentanyl, elicited inhibition of rhythmic spontaneous reflex increases in vesical pressure (VP) evoked by urinary bladder distension. The duration of fentanyl-induced inhibition was dose-related between 0.8 and 8.0 μg/kg i.v. Pretreatment with the opiate receptor antagonist, naloxone HCl (250 μg/kg i.v.), antagonized completely fentanyl's effect on VP rhythm. Results similar to those obtained with fentanyl were observed after the bilateral stimulation of opiate receptors in the dorsolateral tegmental-subceruleus region of the pons (DLT-SC region) with D-Ala2-Met5-enkephalinamide (DAMA) microinjections. These inhibitory effects were dose-related and significant between 1.0 and 100.0 ng/site. DAMA in the DLT-SC did not alter basal cardiorespiratory parameters. The systemic and local administration of naloxone reversed rapidly the VP effects elicited by DAMA in the DLT-SC region. Naloxone alone, administered either i.v. or locally in the DLT-SC region, increased the frequency of spontaneous reflex increases in VP. Moreover, pretreatment of the DLT-SC region with naloxone microinjections significantly (55% reduction) decreased the duration of fentanyl (8.0 μg/kg i.v.)-induced inhibition of VP rhythm. Neurons in DLT-SC region whose discharge increased just before and throughout spontaneous increases in VP (vesical contraction-related units), were inhibited rapidly and completely by the systemic administration of fentanyl. However, fentanyl elicited a prolonged decremental discharge in neurons of the DLT-SC region with discharge patterns related to vesical relaxation (vesical relaxation-related units). The descending vesical motor pathway activated by the microinjection of l-glutamate in the DLT-SC region was not altered by fentanyl. These results indicate that opiate receptors in the DLT-SC region represent a highly sensitive locus of endogenous and exogenous inhibitory opioid action in the micturition reflex arc. Opioid actions in this area of pons may exert differential effects upon the various components of the micturition reflex.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Molecular Medicine