McGovern Medical School, University of Texas Health Science Center, Houston, TX 77006, United States.
Department of Biological Sciences, Chapman University, Orange, CA 92866, United States.
Physiol Behav. 2019 Apr 1;202:77-86. doi: 10.1016/j.physbeh.2018.12.021. Epub 2019 Jan 14.
Chronic use of psychostimulants such as methylphenidate (MPD) and amphetamine (Amph) leads to abuse and dependence. Cross-sensitization occurs when exposure to a drug causes a significant intensified response to a different drug as compared to the effect of the drug in subjects with no previous exposure. Cross-sensitization is used as an experimental correlate for a drug's potential to elicit dependence. The present study uses male and female adolescent rats to examine whether cross-sensitization occurs with MPD, a drug not traditionally considered to elicit dependence, and Amph, a drug considered to elicit dependence. The results showed that there is cross-sensitization with MPD to Amph in adolescent rats and that there is a significant difference in male and female responses. Cross-sensitization between MPD and Amph was observed in a linear dose dependent manner in males and in an inverted U-shape pattern in females. Males treated with the highest dose of 10.0 mg/kg MPD and females treated with the mid-dose of 2.5 mg/kg MPD showed the most robust cross-sensitization. Overall, adolescent female rodents had a greater intensity of response to MPD, Amph, and cross-sensitization between MPD and Amph. This study shows that there are significant sex differences in psychostimulant cross-sensitization in adolescence, indicating the maturity of the gonadal system is not the predominant reason for differences between male and female responses to psychostimulant drugs.
长期使用哌甲酯（MPD）和苯丙胺（Amph）等精神兴奋剂会导致滥用和依赖。当暴露于一种药物会导致对另一种药物的反应明显增强，与未接触过该药物的受试者相比，这种药物的作用更强烈时，就会发生交叉敏感现象。交叉敏感现象被用作一种实验相关性，用于评估药物引发依赖的潜力。本研究使用雄性和雌性青少年大鼠来研究 MPD（一种传统上不被认为会引起依赖的药物）和 Amph（一种被认为会引起依赖的药物）之间是否会发生交叉敏感现象。结果表明，MPD 与 Amph 之间存在交叉敏感现象，而且雄性和雌性的反应存在显著差异。在雄性中，MPD 和 Amph 之间的交叉敏感现象呈线性剂量依赖性，而在雌性中呈倒 U 形模式。接受 10.0mg/kg MPD 最高剂量治疗的雄性和接受 2.5mg/kg MPD 中剂量治疗的雌性表现出最强的交叉敏感现象。总体而言，青少年雌性啮齿动物对 MPD、Amph 和 MPD 与 Amph 之间的交叉敏感现象的反应强度更大。这项研究表明，在青少年中，精神兴奋剂的交叉敏感现象存在显著的性别差异，这表明性腺系统的成熟并不是雄性和雌性对精神兴奋剂药物反应差异的主要原因。
