Role of supraspinal tachykinins for volume- and L-dopa-induced bladder activity in normal conscious rats

To clarify the rules of tachykinins in volume-induced micturition and in bl adder hyperactivity, presumed to originate from supraspinal structures, nor mal, female Sprague-Dawley rats were investigated cystometrically before an d after intracerebroventricular (i.c.v) administration of RP 67,580, a sele ctive antagonist of NK-1 receptors, and/or SR 48,968, a selective antagonis t of NK-2 receptors. The effects of RP 67,580 and SR 48,968 on intraperiton eal (i.p.) L-dopa-induced bladder hyperactivity were also investigated. I.c .v. administration of RP 67,580 (20 nmol) SR 48,968 (20 nmol) suppressed mi cturition. Combination of i.c.v. RP 67,580(2 nmol) and SR 48,968 (2 nmol) s ignificantly decreased micturition pressure (18%), and increased bladder ca pacity (26%), micturition volume (18%), and residual volume (223%). In rats pretreated with i.p. carbidopa 50 mg/kg, i.p. L-dopa 50 mg/kg caused bladd er hyperactivity that was attenuated by the combination of i.c.v. RP 67,580 (2 nmol) and SR 48,968 (2 nmol). The results suggest that tachykinins, via stimulation of NK receptors in supraspinal structures, are involved in bot h volume and L-dopa-induced stimulation of bladder activity. This may imply that tachykinins can influence both the supraspinal and spinal control of the urinary bladder. it also implies that supraspinal NK receptors are a po ssible target for drugs aimed fur elimination of bladder hyperactivity medi ated via these pathways. (C) 2000 Wiley-Liss, Inc.