Neuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, University of Karachi, Pakistan.
National Center for Proteomics, University of Karachi, Karachi, Pakistan.
Behav Brain Res. 2022 Feb 10;418:113660. doi: 10.1016/j.bbr.2021.113660. Epub 2021 Nov 6.
Accumulating studies consistently show that methylphenidate (MPD), the first line drug for treating Attention-Deficit Hyperactivity Disorder (ADHD), is abused by patients to whom the drug is prescribed. Like other psychostimulants, only low doses of MPD improve cognitive performance while higher doses impair it. Preventing the use of high doses of MPD is important for retaining its therapeutic efficacy. Previously, it has been shown that performance in Morris water maze test is improved in rats treated, orally, with MPD in doses of 2.5 mg/kg; but higher doses (5 mg/kg) impair it. The present study is designed to monitor rewarding effects of 2.5 mg/kg MPD in conditioned place preference (CPP) paradigm and its potential inhibition in buspirone co-treated animals. Our results show that rewarding effects of MPD in CPP paradigm are prevented in rats co-treated with buspirone in doses of 0.1 and 0.3 mg/kg. Animals treated with MPD exhibit a downregulation of 5-HT1A receptor mRNA in the nucleus accumbens which is also prevented in rats co-treated with 0.1 and 0.3 mg/kg but not 1.0 and 2.0 mg/kg buspirone. Administration of buspirone in these doses is not rewarding in CPP test and upregulates 5-HT1A receptor mRNA in the nucleus accumbens. The findings suggest that co-use of low doses of buspirone can prevent rewarding effects of MPD to help retain its therapeutic efficacy.
越来越多的研究表明，哌醋甲酯（MPD）是治疗注意力缺陷多动障碍（ADHD）的一线药物，但被开处方的患者会滥用该药物。与其他精神兴奋剂一样，只有低剂量的 MPD 才能提高认知表现，而高剂量则会损害认知表现。防止使用高剂量的 MPD 对于保持其治疗效果很重要。以前已经表明，经口给予大鼠 2.5mg/kg 的 MPD 可改善其在 Morris 水迷宫测试中的表现；但更高剂量（5mg/kg）会损害其表现。本研究旨在监测 2.5mg/kg MPD 在条件性位置偏好（CPP）范式中的奖赏效应及其在丁螺环酮共同治疗动物中的潜在抑制作用。我们的结果表明，在 CPP 范式中，2.5mg/kg MPD 的奖赏效应在与 0.1 和 0.3mg/kg 丁螺环酮共同治疗的大鼠中被阻止。用 MPD 治疗的动物在伏隔核中表现出 5-HT1A 受体 mRNA 的下调，这在与 0.1 和 0.3mg/kg 但不是 1.0 和 2.0mg/kg 丁螺环酮共同治疗的大鼠中也被阻止。在这些剂量下给予丁螺环酮在 CPP 测试中没有奖赏作用，并上调伏隔核中的 5-HT1A 受体 mRNA。这些发现表明，共同使用低剂量的丁螺环酮可以防止 MPD 的奖赏作用，有助于保持其治疗效果。
