EFFECTS OF NEUROKININ RECEPTOR ANTAGONISTS ON L-DOPA INDUCED BLADDER HYPERACTIVITY IN NORMAL CONSCIOUS RATS

Purpose: The urodynamic effects of intrathecal neurokinin (NK) recepto r blockade on L-dopa-induced bladder hyperactivity were investigated i n a rat model. Materials and Methods: Continuous cystometry was perfor med in normal, conscious, female Sprague-Dawley rats. Results: In rats pretreated with intraperitoneal carbidopa 50 mg./kg., intraperitoneal L-dopa 50 mg./kg. caused bladder hyperactivity that could be attenuat ed by intrathecal administration of the NK1 receptor selective antagon ist SR 140,333 (2 nnol.), whereas the NK2 receptor selective antagonis t SR 48,968 (2 nmol.) failed to do so. Combination of SR 140,333 (2 nm ol.) and SR 48,968 (2 nmol.), which by itself decreased micturition pr essure, practically abolished the L-dopa-induced hyperactivity. Conclu sions: The present results suggest that tachykinins, via stimulation o f NK1 (and/or NK2) receptors, are involved in L-dopa-induced Madder hy peractivity, most probably at the spinal level. This implies tachykini n involvement in the supraspinal pathways that control the sacral para sympathetic center innervating the urinary bladder. It also implies th at spinal NK receptors are a possible target for drugs aimed for elimi nation of bladder hyperactivity mediated via these pathways.