Effect of acute or chronic administration of imipramine on spinal and supraspinal micturition reflexes in rats.
Acute imipramine administration (15 mg/kg i.p. 60 min before) increased the threshold for activating the spinal but not the supraspinal vesico-vesical micturition reflex in urethane-anesthetized rats. On the other hand, "chronic" imipramine administration (15 mg/kg i.p./day for 5 consecutive days) increased selectively the threshold of the supraspinal micturition reflex. Intravenous administration of cumulative doses of imipramine (up to 14 mg/kg) exerted a progressive inhibitory effect on the supraspinal reflex and voiding efficiency, possibly related to direct inhibition of muscular contractility at the bladder level. However, with the dose regimen used to compare the action of imipramine on spinal and supraspinal reflexes (15 mg/kg i.p., 60 min before), imipramine did not affect the volume-pressure curve or myogenic activity in decentralized bladders (bilateral removal of pelvic ganglia). The effect of acute imipramine on threshold of the spinal vesico-vesical reflex was absent in rats receiving oral p-chlorophenylalanine to deplete 5-hydroxytryptamine stores in the central nervous system. On the other hand, p-chlorophenylalanine pretreatment did not prevent the action of chronic imipramine administration on the supraspinal reflex. Acute administration of desipramine, the major metabolite of imipramine, increased threshold of the spinal but not supraspinal micturition reflex. These findings indicate that the ability of imipramine to modulate vesico-urethral motility at the central nervous system level may involve different mechanisms. Inhibition of 5-hydroxytryptamine reuptake in nerve terminals may be important for the acute modulatory effect of imipramine on the spinal reflex.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Borsini
F
F
Lecci
A
A
Giuliani
S
S
Meli
P
P
Gragnani
L
L
Meli
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004775:Enuresis / Q000517:prevention & control; D010134:Fenclonine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D014554:Urination / Q000187:drug effects*
D011985:Receptors, Serotonin; D001285:Atropine; D007099:Imipramine; D010134:Fenclonine; D003891:Desipramine