TY - JOUR T1 - Inhibition of Bladder Activity by 5-Hydroxytryptamine<sub>1</sub> Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1266 LP - 1272 DO - 10.1124/jpet.103.063842 VL - 310 IS - 3 AU - Baojun Gu AU - Kenneth J. Olejar AU - Jerome P. Reiter AU - Karl B. Thor AU - Paul C. Dolber Y1 - 2004/09/01 UR - http://jpet.aspetjournals.org/content/310/3/1266.abstract N2 - The serotonin (5-hydroxytryptamine1A) 5-HT1A receptor agonist 8-OH-DPAT [(R)- (+)-8-hydroxy-2-(di-n-propylamino)tetralin] inhibits bladder activity under nociceptive but not innocuous conditions in cats with an intact spinal cord, suggestive of an effect on primary afferent C fibers or their targets. Because C fibers play a key role in reflex micturition in chronic spinal cord injury (SCI), we investigated the effect of 8-OH-DPAT on micturition in SCI cats. We also investigated GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide), which has agonist activity predominantly at 5-HT1B and 5-HT1D receptors but also at the 5-HT1A receptor. Chloralose-anesthetized cats were catheterized through the bladder dome for saline-filling cystometry. Dose-response curves for i.v. 8-OH-DPAT (0.3-30 μg/kg) and GR-46611 (0.03-300 μg/kg) were followed in three cases each by 5-HT1A antagonist WAY-100635 [N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide] at 300 μg/kg. Threshold volume, capacity, residual volume, micturition volume, and arterial pressure were measured. Intact cats showed few significant changes in cystometric variables. SCI cats responded to both 8-OH-DPAT and GR-46611 with dose-dependent increases in threshold volume, capacity, and residual volume, significant at ≥10 μg/kg for 8-OH-DPAT and at ≥3 μg/kg for GR-46611. Effects of 8-OH-DPAT but not GR-46611 were largely reversed by WAY-100635. Both 5-HT1A and 5-HT1B/1D agonists may offer a promising means of reducing bladder hyperactivity and increasing bladder capacity in patients with chronic SCI. The American Society for Pharmacology and Experimental Therapeutics ER -