Alterations in voiding frequency and cystometry in the clomipramine induced model of endogenous depression and reversal with fluoxetine.
OBJECTIVE
Because serotonin (5-HT) in the central nervous system may inhibit bladder activity, we postulated that depression associated with altered 5-HT function might be associated with overactive bladder (OAB). We examined a rat model of endogenous depression caused by lowering 5-HT for effects on voiding frequency (VF) and awake cystometry (CMG), and examined the effect of reversal using the selective serotonin reuptake inhibitor fluoxetine.


METHODS
Wistar rat pups were divided into 2 groups, namely clomipramine treated (CL) and saline control (SC). From postnatal days 8 to 21 each pup was injected with CL hydrochloride (22.5 mg/kg body weight) or an equal volume of saline. VF was assessed at 10 and 15 weeks. Behavioral correlates of depression were assessed using the forced swim test. At age 15 weeks CMG was performed. Fluoxetine (20 mg/kg daily) was administrated to a subset of SC/CL rats, and VF and CMG were repeated.


RESULTS
In CL rats immobility was increased when rats were submitted to the forced swim test, indicating depression. CL rats voided more frequently than the SC group at 10 and 15 weeks but the difference was significant only in females. CMG of female CL group showed decreased bladder capacity, micturition volume and intermicturition contractions compared with the SC group. Treatment with fluoxetine reversed these changes, as in SC rats.


CONCLUSIONS
These results support the hypothesis that OAB in a subgroup of depressed individuals may be associated with altered 5-HT function. It may explain reports of an association between depression and OAB.
Lee
Kyu-Sung
KS
Department of Urology, Sungkyunkwan University School of Medicine, Seoul, Korea.
Na
Yong-Gil
YG
Dean-McKinney
Travis
T
Klausner
Adam P
AP
Tuttle
Jeremy B
JB
Steers
William D
WD
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002997:Clomipramine; D003866:Depressive Disorder / Q000139:chemically induced / Q000503:physiopathology*; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006380:Helplessness, Learned; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012737:Sex Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D014555:Urination Disorders / Q000139:chemically induced / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology*
D018687:Antidepressive Agents, Second-Generation; D002997:Clomipramine; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors