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GABAergic modulation of micturition behavior in freely moving rats

, : GABAergic modulation of micturition behavior in freely moving rats. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 189 7

Pre-clinical and in-vitro studies suggest that baclofen, a GABAB agonist, may be useful for the treatment of urinary incontinence. However, the contribution of GABA-ergic neurotransmission on the micturition reflex has only been evaluated in anesthetized and/or operated animals. Thus, using metabolic cages, we evaluated GABA-ergic contribution to normal micturition, in naive freely moving female rats, with diuresis (total voided volume) and bladder continence (micturition frequency and mean void volume/event) as end points. Intrathecal administration of baclofen (0.5 mug in 10 mul aCSF) produced diuresis only; the mean void volume remained unaffected. Following subcutaneous administration however, baclofen (2.0-5.0 mg/kg) induced, in addition to its diuretic effect, a significant increase of the mean void volume. The baclofen-induced increase in bladder continence, not diuresis, could be antagonized by CGP52432 (10 mg/kg, sc), a GABAB specific antagonist that does not cross the blood-brain barrier. These data suggest that peripheral GABAB receptor activation is responsible for increasing bladder capacity whereas central GABAB receptor activation plays a role in diuresis. To rule out any involvement of GABAA receptors in micturition, we further evaluated the effect of a GABAA antagonist (bicuculline 1.0 mg/kg, sc) as a pre-treatment to modulate baclofen effects. In these conditions we observed a modest reduction of the baclofen-induced diuresis. These data demonstrate the involvement of GABAB in bladder continence in the conscious animal.


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