Department of Psychology, Occidental College, Los Angeles, CA 90041, USA.
Pharmacol Biochem Behav. 2011 Jan;97(3):500-8. doi: 10.1016/j.pbb.2010.10.009. Epub 2010 Oct 29.
Behavioral effects of the same dose of the same drug can vary in degree and direction between and within individuals. The present study examines behavioral base rates, feeding status, and dispositional differences as sources of inter- and intra-individual heterogeneity in drug response. Modulation of the effects of methylphenidate (MPD) on wheel running and acoustic startle by food deprivation was examined in three experiments. Freely fed or food deprived Harlan Sprague-Dawley rats (running study) or rats selectively bred for low (LoS) and high (HiS) saccharin intake (running and startle studies) were given MPD (10 mg/kg) or saline before testing. Overall drug effects and predictors of drug response were assessed. MPD increased running and startle amplitude and disrupted prepulse inhibition; systematic variation among rats of these effects and their modulation by food deprivation was observed. Deprivation-induced running predicted MPD's effect in Harlan SD and LoS rats. Observation of this relationship among commercial rats suggests that acute deprivation sensitivity has utility as a noninvasive marker for drug responses. Its observation in rats selected on a taste phenotype with known correlates points to fruitful avenues of research on stimulant drugs' mechanisms, especially in dopaminergic pathways, and may be relevant to their clinical usage.
同一剂量、同一药物的行为效应在个体间和个体内可能在程度和方向上有所不同。本研究探讨了行为基础率、进食状态和性格差异作为药物反应个体间和个体内异质性的来源。在三个实验中，研究了禁食对哌甲酯（MPD）对轮跑和声音惊吓反应的影响。自由喂食或禁食的哈兰斯普拉格-道利大鼠（跑步研究）或选择性饲养的低（LoS）和高（HiS）糖精摄入量的大鼠（跑步和惊吓研究）在测试前给予 MPD（10mg/kg）或生理盐水。评估了药物的整体效果和药物反应的预测因素。MPD 增加了跑动和惊跳幅度，并破坏了前脉冲抑制；在这些效应及其对禁食的调节方面，观察到了大鼠之间的系统变化。禁食引起的跑动预测了哈兰 SD 和 LoS 大鼠对 MPD 的反应。在商业大鼠中观察到这种关系表明，急性剥夺敏感性可作为药物反应的非侵入性标志物。在具有已知相关性的味觉表型上选择的大鼠中观察到这一点，为研究兴奋剂药物的机制，特别是在多巴胺能途径方面，开辟了富有成效的途径，并且可能与它们的临床应用有关。
