| Abstract: | 長期增益現象被認為是一種藉由在興奮性突觸接由一個傳入纖維強的重覆性刺激作用而產生的長期持久性增加作用。在過去二十年，長期增益現象在海馬回的CA1 區域被廣泛地研究，因為它被認為是學習與記憶形成的一個根本機制。尿液貯存是膀胱的一個重要功能。在排尿週期之尿液貯存階段期間，膀胱膨脹所引發的感覺神經衝動經由骨盆傳入纖維向心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，而最後導致外在尿道括約肌的收縮。這骨盆尿道反射是使尿道發展足夠的阻抗機制以維護尿液自制所必須的。關於骨盆尿道反射活性的最近研究顯示骨盆傳入纖維的重覆性或強直性刺激會誘導一個在骨盆尿道反射活性明顯且持久的增益現象。首先先給予1/30赫茲作為單一刺激誘發出一個骨盆神經-尿道反射的反射現象，接著改成1赫茲的重複性刺激以誘發出增益現象。脊髓腔內注射L-glutamate (100 μM, 10 μl)及NMDA (100 μM, 10 μl)，為glutamate接受器的作用劑，在單一刺激下發現產生脊髓反射增益現象(Spinal reflex potentiation; SRP)，而在脊髓腔內注射CNQX (100 μM, 10 μl)及APV (100 μM, 10 μl)，為glutamate接受器的拮抗劑，在重複性刺激下發現SRP有被抑制的情形。此外，我們研究是否安非他命能夠影響骨盆尿道反射的可塑性及闡明安非他命在排尿功能之作用中神經傳遞物質所參與之角色。在脊髓腔內注射安非他命 (100 μM, 10 μl)，在單一刺激下發現產生SRP，接著在脊髓腔內注射H89 (10 μM, 10 μl)，為蛋白激酶A (PKA)抑制劑，發現SRP有被抑制住的情形。這些研究結果顯示骨盆神經-尿道反射的反射現象為NMDA依賴性之反射現象，且安非他命成癮者所造成阻塞性膀胱官能不良的情形可能是藉由活化PKA路徑來產生調控。
Long-term potentiation (LTP) is characterized by a long lasting enhancement in the efficacy of the excitatory synapse following a strong repetitive stimulation of input fibers. LTP in the CA1 area of the hippocampus has been investigated extensively in the past two decades because it is considered as a fundamental mechanism of learning and memory formation. Urine storage is an important function of the urinary bladder. During the storage phase of the micturition cycle, sensory impulses induced by bladder distension transmit centripetally onto the neurons of the dorsal horn through the pelvic afferent fibers. After integration within the spinal cord, motor impulses travel through the pudendal efferent fibers and finally cause contractions of the external urethral sphincter. This pelvic-urethral reflex (PUR) is essential for the urethra to develop sufficient resistance to maintain urine continence. Recent studies on PUR activities have shown repetitive/titanic stimulation of the pelvic afferent fibers induced a distinct and long-lasting potentiation in PUR activities. When compared with test stimulation (1/30 Hz) evoked a baseline reflex activity with a single action potential, repetitive stimulation (1 Hz) induced spinal reflex potentiation (SRP) in the reflex activity. Intrathecal L-glutamate (100 μM, 10 μl) and NMDA (100 μM, 10 μl), glutamate receptor agonists, induced excitatory effects on the test stimulation (TS, 1/30 Hz) elicited reflex activity. Intrathecal CNQX (100 μM, 10 μl) and APV (100 μM, 10 μl), glutamate receptor antagonists, exhibited inhibitory effects on the RS-induced SRP. In addition, we investigate whether d-amphetamine may affect PUR plasticity and the possible neurotransmitters involved to clarify the effects of d-amphetamine on miturition functions. Intrathecal d-amphetamine (100 μM, 10 μl) induced excitatory effects on the test stimulation (TS, 1/30 Hz) elicited reflex activity. Exhibited inhibitory effects reversed by intrathecal H89 (10 μM, 10 μl), a protein kinase A (PKA) inhibitor. These findings suggested suggested this stimulation-induced potentiation was glutamatergic NMDA receptor-dependent, and the obstructive bladder dysfunction induced by amphetamine addicts may triggered by the PKA activation activating. |
