Department of Physiology & Pharmacology, College of Veterinary Medicine, 501 D.W. Brooks Drive, Athens, GA 30602-7389, USA.
Behav Brain Res. 2013 Sep 1;252:444-9. doi: 10.1016/j.bbr.2013.06.026. Epub 2013 Jun 21.
With respect to the treatment of addiction, the objective of extinction training is to decrease drug-seeking behavior by repeatedly exposing the patient to cues in the absence of unconditioned reinforcement. Such exposure therapy typically takes place in a novel (clinical) environment. This is potentially problematic, as the effects of extinction training include a context dependent component and therefore diminished efficacy is expected upon the patient's return to former drug-seeking/taking environments. We have reported that treatment with the NMDAR coagonist d-serine is effective in facilitating the effects of extinction to reduce cocaine-primed reinstatement. The present study assesses d-serine's effectiveness in reducing drug-primed reinstatement under conditions in which extinction training occurs in a novel environment. After 22 days of cocaine self-administration (0.5 mg/kg) in context "A", animals underwent 5 extinction training sessions in context "B". Immediately after each extinction session in "B", animals received either saline or d-serine (60 mg/kg) treatment. Our results indicate that d-serine treatment following extinction in "B" had no effect on either IV or IP cocaine-primed reinstatement conducted in "A". These results stand in contrast to our previous findings where extinction occurred in "A", indicating that d-serine's effectiveness in facilitating extinction training to reduce drug-primed reinstatement is not transferable to a novel extinction environment. This inability of d-serine treatment to reduce the context specificity of extinction training may explain the inconsistent effects observed in clinical studies published to date in which adjunctive cognitive enhancement treatment has been combined with behavioral therapy without significant benefit.
关于成瘾的治疗，灭绝训练的目的是通过反复暴露于无条件强化的线索来减少觅药行为。这种暴露疗法通常发生在一个新颖的（临床）环境中。这可能是有问题的，因为灭绝训练的效果包括一个与情境相关的成分，因此预计当患者回到以前的觅药/用药环境时，效果会减弱。我们已经报告说，使用 NMDA 共激动剂 D-丝氨酸可以有效地促进灭绝的效果，从而减少可卡因引发的复吸。本研究评估了 D-丝氨酸在灭绝训练发生在新环境中的情况下减少药物引发复吸的效果。在“ A”环境中进行 22 天可卡因自我给药（0.5mg/kg）后，动物在“ B”环境中进行了 5 次灭绝训练。在“ B”中的每次灭绝训练后，动物立即接受盐水或 D-丝氨酸（60mg/kg）治疗。我们的结果表明，D-丝氨酸在“ B”中进行灭绝训练后的治疗对在“ A”中进行的 IV 或 IP 可卡因引发的复吸没有影响。这些结果与我们之前的发现形成对比，表明 D-丝氨酸促进灭绝训练以减少药物引发复吸的有效性不能转移到新的灭绝环境。D-丝氨酸治疗不能减少灭绝训练的情境特异性可能解释了迄今为止在临床研究中观察到的不一致效果，其中附加认知增强治疗与行为治疗相结合，但没有显著益处。
