Suppression of the micturition reflex in urethane-anesthetized rats by intracerebroventricular injection of WAY100635, a 5-HT_1A receptor antagonist

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• 作者：Yoshiyama ; Mitsuharu ; Kakizaki ; Hidehiro ; de Groat ; William C.
• 关键词：Endocrine and autonomic regulation ; Gastrointestinal and urogenital regulation ; Afferent pathway ; Parasympathetic reflex ; Urinary bladder ; Raphe nucleus ; Serotonin receptor
• 刊名：Brain Research
• 出版年：2003
• 出版时间：August 8, 2003
• 年：2003
• 卷：980
• 期：2
• 页码：281-287
• 全文大小：186 K

文摘

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 μg), 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 μg) increased the interval between contractions but only slightly reduced the amplitude of the contractions. However, 100 μg 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 μg, 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.