Appenrodt Edgar, Schwarzberg Helmut
Institute of Neurophysiology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Pharmacol Biochem Behav. 2003 Apr;75(1):67-73. doi: 10.1016/s0091-3057(03)00037-6.
Methylphenidate (MPH), a dopamine (DA) reuptake inhibitor, is well known to enhance motor activity, in part depending on the time of its application during the light-dark cycle. Moreover, after MPH administration, the hypothalamo-neurohypophysial axis including the neuropeptide vasopressin (AVP) was found influenced. Both the latter and behavioural effects of central AVP can also be modulated by the pineal gland with its light-dark-dependent activity. The present study was performed to investigate whether the pineal gland, its hormone melatonin (Mel), and AVP are involved in the MPH-evoked stimulation of activity. After application of 10 mg/kg MPH, the motor activity in pinealectomised (PE) rats was significantly higher than in sham-operated (SO) animals. After application of 250 microg Mel before MPH treatment, the stimulation of motor activity was diminished in PE rats and augmented in SO animals; however, when SO and PE rats were compared after Mel pretreatment, the reaction to MPH was nearly identical. Blocking the endogenous AVP by 25 or 1 microg of the V1a receptor antagonist d(CH(2))(5)[Tyr(Me)(2)]AVP (AAVP) before MPH treatment significantly augmented the motor activity in SO rats only and abolished the differences seen between SO and PE animals after MPH application. The present results indicate that the behavioural stimulation of MPH was modulated by both the pineal gland with its hormone Mel as well as the neuropeptide AVP.
哌甲酯（MPH）是一种多巴胺（DA）再摄取抑制剂，众所周知它能增强运动活性，部分取决于其在昼夜循环中给药的时间。此外，在给予MPH后，发现包括神经肽血管加压素（AVP）在内的下丘脑-神经垂体轴受到影响。中枢AVP的后一种作用和行为效应也可由具有昼夜依赖性活动的松果体调节。本研究旨在探讨松果体及其激素褪黑素（Mel）和AVP是否参与MPH引起的活动刺激。给予10mg/kg MPH后，松果体切除（PE）大鼠的运动活性显著高于假手术（SO）动物。在MPH治疗前给予250μg Mel后，PE大鼠的运动活性刺激减弱，SO动物增强；然而，当比较Mel预处理后的SO和PE大鼠时，对MPH的反应几乎相同。在MPH治疗前，用25或1μg V1a受体拮抗剂d(CH(2))(5)[Tyr(Me)(2)]AVP（AAVP）阻断内源性AVP，仅显著增强了SO大鼠的运动活性，并消除了MPH给药后SO和PE动物之间的差异。目前的结果表明，MPH的行为刺激受到松果体及其激素Mel以及神经肽AVP的调节。
