Wooters T E, Dwoskin L P, Bardo M T
Department of Psychology, BBSRB, University of Kentucky, Lexington, KY 40536-0509, USA.
Psychopharmacology (Berl). 2006 Sep;188(1):18-27. doi: 10.1007/s00213-006-0445-9. Epub 2006 Aug 2.
Rats displaying high levels of activity in an inescapable novel environment (high responders; HR) are more sensitive to the locomotor effect of stimulant drugs than rats displaying low levels of activity (low responders; LR).
The current study determined the age- and sex-dependent locomotor effects of repeated methylphenidate in HR and LR rats.
Periadolescent and adult male and female Sprague-Dawley rats were first classified as HR or LR; rats were also classified as high or low novelty seekers based on free-choice preference for a novel environment. Locomotor activity was subsequently assessed after ten daily injections of methylphenidate (3 or 10 mg/kg s.c.) or saline. Fifteen days later, rats were challenged with saline and methylphenidate (10 mg/kg) over 2 days.
During the repeated methylphenidate treatment phase, adult females showed greater methylphenidate-induced hyperactivity than adult males; there was no reliable difference in methylphenidate-induced hyperactivity between HR and LR rats of either age or sex. However, periadolescent male HR rats given repeated methylphenidate showed greater conditioned hyperactivity after the saline challenge than periadolescent male LR rats. Further, adult female HR rats given repeated methylphenidate showed greater conditioned hyperactivity and sensitization than adult female LR rats. In contrast, although free-choice novelty preference was greater among periadolescents than adults, individual differences in this variable did not predict the effect of repeated methylphenidate during any phase of the experiment.
Although individual differences in response to inescapable novelty predict methylphenidate-induced conditioned hyperactivity and sensitization, this relationship is moderated by age and sex.
在无法逃避的新环境中表现出高活动水平的大鼠（高反应者；HR）比表现出低活动水平的大鼠（低反应者；LR）对兴奋剂药物的运动效应更敏感。
本研究确定了重复给予哌醋甲酯对HR和LR大鼠的年龄和性别依赖性运动效应。
将青春期前后及成年的雄性和雌性Sprague-Dawley大鼠首先分为HR或LR；还根据对新环境的自由选择偏好将大鼠分为高或低新奇寻求者。随后在每天注射十次哌醋甲酯（3或10mg/kg皮下注射）或生理盐水后评估运动活动。15天后，在2天内用生理盐水和哌醋甲酯（10mg/kg）对大鼠进行激发试验。
在重复给予哌醋甲酯的治疗阶段，成年雌性大鼠比成年雄性大鼠表现出更大的哌醋甲酯诱导的多动；任何年龄或性别的HR和LR大鼠在哌醋甲酯诱导的多动方面均无可靠差异。然而，重复给予哌醋甲酯的青春期前雄性HR大鼠在生理盐水激发试验后比青春期前雄性LR大鼠表现出更大的条件性多动。此外，重复给予哌醋甲酯的成年雌性HR大鼠比成年雌性LR大鼠表现出更大的条件性多动和敏感化。相比之下，尽管青春期前大鼠的自由选择新奇偏好高于成年大鼠，但该变量的个体差异并未预测重复给予哌醋甲酯在实验任何阶段的效果。
尽管对无法逃避的新奇事物的反应个体差异可预测哌醋甲酯诱导的条件性多动和敏感化，但这种关系受年龄和性别的调节。
