Senior Daniela, McCarthy Madison, Ahmed Rania, Klein Shannon, Lee Wen Xuan, Hadjiargyrou Michael, Komatsu David, Steiner Heinz, Thanos Panayotis K
Behavioral Neuropharmacology and Neuroimaging Laboratory (BNNL), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14051, USA.
Department of Psychology, University at Buffalo, Buffalo, NY, 14203, USA.
Addict Neurosci. 2023 Dec;8. doi: 10.1016/j.addicn.2023.100127. Epub 2023 Aug 26.
Depression and attention deficit hyperactivity disorder are known to be comorbid. Treatment of these commonly coexisting diseases typically involves the combined prescription of methylphenidate (MP), a psychostimulant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI). MP and cocaine have similar mechanisms of action and this study examined the effects of chronic treatment of MP combined with FLX on cocaine consumption in rats.
Four groups of rats received access to drinking solutions of water (control), MP (30/60 mg/kg/day), FLX (20 mg/kg/day), or the combination of MP (30/60 mg/kg/day) plus FLX (20 mg/kg/day), during 8 h per day for one month. Following these drug treatments, rats were allowed to self-administer cocaine for 14 days.
Our results showed that, during the first week of cocaine self-administration, the MP-treated rats had significantly greater numbers of active lever presses (plus 127%) and increased consumption of cocaine compared to the control rats. In contrast, during week two of cocaine self-administration, the rats treated with the MP + FLX combination showed significantly more lever presses (plus 198%) and significantly greater cocaine consumption (plus 84%) compared to the water controls.
Chronic oral treatment during adolescence with the combination of MP plus FLX resulted in increased cocaine use after 2 weeks of cocaine self-administration in rats. These novel findings suggest that the combined exposure to these two drugs chronically, during adolescence, may produce increased vulnerability towards cocaine abuse during young adulthood.
抑郁症和注意力缺陷多动障碍已知会共病。治疗这些常见的共存疾病通常涉及联合使用精神振奋剂哌甲酯(MP)和选择性5-羟色胺再摄取抑制剂(SSRI)氟西汀(FLX)进行处方。MP和可卡因具有相似的作用机制,本研究检测了MP联合FLX长期治疗对大鼠可卡因摄入量的影响。
四组大鼠每天有8小时可获取水(对照组)、MP(30/60毫克/千克/天)、FLX(20毫克/千克/天)或MP(30/60毫克/千克/天)加FLX(20毫克/千克/天)的饮用溶液,持续一个月。在这些药物治疗后,让大鼠自行服用可卡因14天。
我们的结果显示,在自行服用可卡因的第一周,与对照大鼠相比,接受MP治疗的大鼠主动按压杠杆的次数显著更多(增加了127%),可卡因摄入量增加。相比之下,在自行服用可卡因的第二周,与饮水对照组相比,接受MP+FLX联合治疗的大鼠按压杠杆的次数显著更多(增加了198%),可卡因摄入量显著更高(增加了84%)。
青春期长期口服MP加FLX联合用药,会导致大鼠在自行服用可卡因2周后可卡因使用量增加。这些新发现表明,青春期长期联合接触这两种药物,可能会使青年期对可卡因滥用的易感性增加。