安非他命、甲基安非他命及俗稱快樂丸的MDMA皆歸類於安非他命類的中樞興奮劑。安非他命類的中樞興奮劑能誘導多種周邊及中樞神經系統作用，如：欣快感、提升自信心、維持精力充沛與降低食慾。因為他們有效的欣快感作用所以導致廣泛的藥物濫用情形發生。長期服用安非他命與快樂丸發現會造成神經性膀胱與尿液滯留。有趣的是就算停用這些藥物，尿液滯留的情形仍會存在。而這導致長期尿液滯留作用的機轉仍不清楚。尿液貯存是膀胱的一個重要功能，當膀胱充滿尿液，膀胱壁上機械性接受器將會被興奮並且引發動作電位的產生。此引發的神經衝動經由骨盆傳入纖維傳送至背角的神經元；訊息在脊髓內整合之後, 經由陰部傳出纖維傳導出運動神經衝動，最後導致外尿道括約肌的收縮。我們最近研究安非他命在麻醉大鼠中藉由骨盆傳入纖維與尿道間之骨盆尿道反射的可塑性上外尿道括約肌活性的作用。研究結果發現脊髓內注射安非他命後給予單一刺激能增加陰部傳出纖維與外尿道括約肌活性的動作電位頻率，此結果可能可以解釋服用安非他命所造成人體慢性尿液滯留的情況。因此，本研究將進一步探討安非他命與快樂丸在單一刺激所誘發的骨盆尿道反射下的長期增益現象，我們也將探討引發此現象可能涵蓋的神經傳遞物質與第二傳訊物質。此外，我們亦將使用脊髓切片與全細胞箝制技術測試安非他命與快樂丸是否會影響長期增益現象。本研究完成後，安非他命類的中樞興奮劑在骨盆傳入纖維間之骨盆尿道反射可塑性的作用將被釐清。這結果可能可以提供治療安非他命類的中樞興奮劑所造成尿液滯留現象的一項有用的資訊。 Amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), are categorized within the group of amphetamine-type stimulants. Amphetamine-type stimulants induce numerous peripheral and central effects, such as feelings of euphoria, heightened self-confidence, sustained high energy levels and decreased appetite. Due to their potent euphoric properties, they are widely abused. Chronic AMPH or MDMA intake has been reported to lead to neurogenic bladder and chronic urinary retention. Of particular interest is the persistence of urinary retention despite the cessation of these drugs. The mechanism underlying the persistent urinary retention is not clear. Urine storage is one of the main functions of urinary bladder. As the bladder is filled, mechanoreceptors on the bladder wall are excited and generate action potentials. These impulses then transmit centripetally into dorsal horn neurons through the pelvic afferent nerve (PAN); after integration within the spinal cord the impulses excite the external urethral sphinctor (EUS) and result in its contraction via the pudendal efferent nerve (PEN). We recently have examined the effects of AMPH on the reflex plasticity between pelvic afferent nerve (PAN) and pudendal efferent nerve (PEN), as well as external-urethral sphincter (EUS) activity in anesthetized rats. A progressive increase in the number of evoked action potentials per stimulus occurred in PEN and EUS activity when amphetamine was intrathecally administered. These effects could explain the reason why AMPH intake leads to chronic urine retention in humans. Therefore, the aims of the present study are to further characterize the profile that intrathecal administration of AMPH and MDMA induced a long-lasting reflex potentiation in TS-induced reflex activity. We will also explore the possible neurotransmitters and second messengers involved. In addition, we will test whether AMPH and MDMA affect long-term potentiation using spinal cord slices and whole-cell patch clamp technique. After completion of the project, the effects of amphetamine-like stimulants on the reflex plasticity between pelvic afferent nerve (PAN) and pudendal efferent nerve (PEN) will be clarified. The results may provide useful information as to how to treat urine retention induced by amphetamine-like stimulants.
