Suppression of the micturition reflex in urethane-anesthetized rats by intracerebroventricular injection of WAY100635, a 5-HT(1A) receptor antagonist.
The influence of supraspinal 5-HT(1A) receptors on reflex bladder activity was evaluated in anesthetized rats by studying the effects of intracerebroventricular (i.c.v.) administration of WAY100635 (1-100 microg), a selective 5-HT(1A) receptor antagonist. The drug dose-dependently decreased the frequency and/or amplitude of isovolumetric reflex bladder contractions. Low doses (1-10 microg) increased the interval between contractions but only slightly reduced the amplitude of the contractions. However, 100 microg of WAY100635 elicited an initial complete block of bladder reflexes followed by a recovery period lasting 10-15 min during which the frequency of reflex contractions was normal but the amplitude was markedly suppressed by 70-80%. Mesulergine (0.1 mg/kg, i.v.), a 5-HT(2C) antagonist, which transiently eliminated bladder activity in some rats (five of 11), blocked the inhibitory effect of WAY100635 (10 or 100 microg, i.c.v.) in only two of six rats. Our data coupled with the results of previous studies suggest that spinal and supraspinal 5-HT(1A) receptors are involved in multiple inhibitory mechanisms controlling the spinobulbospinal micturition reflex pathway. The regulation of the frequency of bladder reflexes is presumably mediated by a suppression of afferent input to the micturition switching circuitry in the pons, whereas the regulation of bladder contraction amplitude may be related to an inhibition of the output from the pons to the parasympathetic nucleus in the spinal cord.
Yoshiyama
Mitsuharu
M
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. pxn15164@nifty.ne.jp
Kakizaki
Hidehiro
H
de Groat
William C
WC
D018686:Anesthetics, Intravenous; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D010879:Piperazines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D014520:Urethane; D014554:Urination / Q000187:drug effects* / Q000502:physiology
D018686:Anesthetics, Intravenous; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D014520:Urethane; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide