Bjork J M, Gaytan O, Patt N, Swann A C, Dafny N
Department of Neurobiology and Anatomy, University of Texas-Houston, Medical School of Houston, 77025, USA.
Int J Neurosci. 1998 Apr;93(3-4):163-79. doi: 10.3109/00207459808986421.
The objective of this study was to characterize the lasting effects of fluoxetine on the locomotor behavior of rats using a computerized activity-monitoring system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the dark phase resulted in dose-dependent suppression of locomotor activity for 4 h following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine administration for the next five days resulted in decreasing locomotor activity during the multiple-administration period relative to saline control. Circadian activity patterns at the conclusion of the regimen were unchanged in shape, but featured uniform decreases in locomotor activity at every hour which were more significant during the phase. Upon discontinuation, fluoxetine-treated rats showed a significant increase in activity during the first 4 h following the first "missed" dose which was not seen in subsequent washout. Ninety-six h after the final maintenance dose, the initial three dosages were readministered, and the locomotor activity suppression in response to the rechallenge dose of fluoxetine was significantly lessened compared to initial challenge. These findings suggest that tolerance and withdrawal were obtained.
本研究的目的是使用计算机化活动监测系统来描述氟西汀对大鼠运动行为的持久影响。在黑暗期2小时时腹腔注射挑战剂量（8、16和24毫克/千克）的氟西汀，导致注射后4小时内运动活动受到剂量依赖性抑制。在接下来的五天中，每天半量递增（10 - 30毫克/千克腹腔注射）氟西汀，相对于生理盐水对照组，在多次给药期间运动活动减少。给药方案结束时的昼夜活动模式形状未改变，但每小时的运动活动均呈现均匀下降，在该阶段更为显著。停药后，接受氟西汀治疗的大鼠在首次“错过”剂量后的最初4小时内活动显著增加，而在随后的洗脱期未观察到这种情况。在最后维持剂量96小时后，重新给予最初的三个剂量，与最初的挑战相比，氟西汀再激发剂量引起的运动活动抑制明显减轻。这些发现表明产生了耐受性和戒断反应。
