Department of Psychology, California State University San Bernardino, San Bernardino, CA 92407, United States of America.
Department of Psychology, California State University San Bernardino, San Bernardino, CA 92407, United States of America.
Pharmacol Biochem Behav. 2022 Jul;218:173424. doi: 10.1016/j.pbb.2022.173424. Epub 2022 Jun 30.
Prescription psychostimulants, such as methylphenidate (MPH), have served as a first line treatment for ADHD and associated developmental disorders since 1961. Psychostimulants has been shown to improve attention, response inhibition, and reduce hyperactivity in patients with ADHD, as well as in non-clinical human populations and animals. While there is a considerable amount of preclinical research investigating the effects of stimulant medications on reward sensitivity and basic learning in male rats, less is understood about their effects in females. Further, there are competing theories on the long-term cognitive impact of MPH, specifically in children who do not have ADHD. To this end, Long-Evans female and male rats were exposed to methylphenidate (0, 2.5, 5 mg/kg, BID, IP) for 20 days during early development (PD10-29). After discontinuation of MPH into adulthood, rats (beginning PD 60) were trained and tested for risk-preference using a 2-choice probabilistic discounting task. For this task, rats were given an option between a 'large-risky' choice (3 sugar pellets delivered on a probabilistic VR schedule) and 'small-certain' choice (1 sugar pellet delivered on a FR schedule). Rats were subsequently tested on an open field conflict test. The results demonstrate that prepubertal exposure to MPH can have lasting effects on decision-making. Specifically, female rats treated with 2.5 mg/kg MPH displayed a decrease in preference for the risky option, whereas male rats treated with the same dose showed an overall increase in preference compared to sex-matched controls. Irrespective of sex, rats treated with 2.5 mg/kg MPH also demonstrated a decrease in anxiety/inhibitory behavior on the modified open field test compared to controls. These results were not due to differences in locomotor behavior. Overall, the study contributes to the growing body of evidence to suggest that MPH exposure early in development can have a sex-dependent impact on decision-making in adulthood.
处方类精神兴奋剂，如哌醋甲酯（MPH），自 1961 年以来一直是治疗 ADHD 和相关发育障碍的一线药物。精神兴奋剂已被证明可改善 ADHD 患者以及非临床人群和动物的注意力、反应抑制和减少多动。虽然有大量的临床前研究调查了兴奋剂药物对雄性大鼠奖赏敏感性和基本学习的影响，但对雌性大鼠的影响了解较少。此外，关于 MPH 的长期认知影响存在相互竞争的理论，特别是在没有 ADHD 的儿童中。为此，长耳雌性和雄性大鼠在早期发育期间（PD10-29）每天两次腹膜内注射接受哌醋甲酯（0、2.5、5mg/kg）治疗 20 天。停止 MPH 进入成年期后，大鼠（从 PD60 开始）接受风险偏好的训练和测试，使用 2 选择概率折扣任务。对于此任务，大鼠可以选择“大风险”选项（根据概率 VR 时间表交付 3 个糖丸）和“小确定”选项（根据 FR 时间表交付 1 个糖丸）。随后，大鼠在开阔场冲突测试中进行测试。结果表明，青春期前暴露于 MPH 可能对决策产生持久影响。具体而言，接受 2.5mg/kg MPH 治疗的雌性大鼠对风险选项的偏好降低，而接受相同剂量治疗的雄性大鼠与性别匹配的对照组相比，整体偏好增加。无论性别如何，接受 2.5mg/kg MPH 治疗的大鼠在改良的开阔场测试中的焦虑/抑制行为也减少。这些结果不是由于运动行为的差异所致。总体而言，该研究有助于越来越多的证据表明，早期发育期间暴露于 MPH 可能对成年期的决策产生性别依赖性影响。
