Talishinsky Aleksandr D, Nicolas Celine, Ikemoto Satoshi
Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd., Suite 200, Baltimore, MD, USA.
Psychopharmacology (Berl). 2017 Jul;234(14):2197-2206. doi: 10.1007/s00213-017-4625-6. Epub 2017 Apr 8.
It is necessary to understand better how chronic food restriction (CFR) and psychostimulant drugs interact in motivated behavior unrelated to food or energy homeostasis.
We examined whether CFR augments methylphenidate (MPH)-potentiated responding reinforced by visual sensation (VS) and whether repeated MPH injections or prolonged CFR further augments such responses.
Before starting the following experiments, rats on a CFR diet received a limited daily ration in such a way that their body weights decreased to 85-90% of their original weights over 2 weeks. In experiment 1, rats on CFR and ad libitum diet received four injections of varying MPH doses (0, 2.5, 5, and 10 mg/kg). In experiment 2, CFR and ad libitum groups received repeated injections of MPH (2.5 mg/kg). In experiment 3, half of CFR rats received repeated injections of MPH (2.5 mg/kg), and the other half received saline, and following a 7-day abstinence, they all received the 2.5-mg/kg dose of MPH.
CFR rats increased VS-reinforced responding more than ad libitum rats when they received MPH. Repeated injections of MPH with prolonged CFR further increased VS-reinforced responding. We found a double dissociation where prolonged CFR (3 vs. 6 weeks) made VS-reinforced responding, but not locomotor activity, more responsive to MPH, whereas repeated MPH injections made locomotor activity, but not VS-reinforced responding, more responsive to MPH.
CFR markedly potentiates effects of MPH on VS-reinforced responding. The present study demonstrates that the longer CFR continues, the greater psychostimulant drugs augment behavioral interaction with salient stimuli.
有必要更深入地了解慢性食物限制(CFR)与精神兴奋药物在与食物或能量稳态无关的动机行为中是如何相互作用的。
我们研究了CFR是否增强了视觉刺激(VS)强化的哌醋甲酯(MPH)增强反应,以及重复注射MPH或长期CFR是否会进一步增强此类反应。
在开始以下实验之前,采用CFR饮食的大鼠每天限量进食,使其体重在2周内降至原始体重的85-90%。在实验1中,采用CFR饮食和自由进食的大鼠接受了四次不同剂量的MPH注射(0、2.5、5和10mg/kg)。在实验2中,CFR组和自由进食组接受了重复注射MPH(2.5mg/kg)。在实验3中,一半的CFR大鼠接受了重复注射MPH(2.5mg/kg),另一半接受了生理盐水注射,在禁欲7天后,它们都接受了2.5mg/kg剂量的MPH。
接受MPH时,CFR大鼠比自由进食大鼠更能增强VS强化反应。重复注射MPH并延长CFR时间进一步增强了VS强化反应。我们发现了一种双重分离现象,即延长CFR(3周与6周)使VS强化反应而非运动活动对MPH更敏感,而重复注射MPH使运动活动而非VS强化反应对MPH更敏感。
CFR显著增强了MPH对VS强化反应的作用。本研究表明,CFR持续时间越长,精神兴奋药物增强与显著刺激的行为相互作用的程度就越大。