Schippers Maria C, Gaastra Mathijs, Mesman Tanja, Schetters Dustin, van Mourik Yvar, Denys Damiaan, Pattij Tommy, De Vries Taco J
Department of Anatomy & Neurosciences, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Department of Psychiatry, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Brain Neurosci Adv. 2017 Jun 1;1:2398212817711083. doi: 10.1177/2398212817711083. eCollection 2017 Jan-Dec.
Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats.
NAcore and NAshell deep brain stimulation was applied during 25 or 100 µg/kg/infusion heroin self-administration on an FR4 schedule of reinforcement and during cue- and heroin-induced reinstatement. In a separate group, effects of NAcore deep brain stimulation on heroin self-administration on a progressive ratio schedule and the first extinction session were examined.
NAcore and NAshell deep brain stimulation did not alter heroin self-administration on an FR4 schedule. NAcore deep brain stimulation decreased cue - but not drug-induced reinstatement of heroin seeking, whereas NAshell deep brain stimulation did not affect reinstatement responding. In the second experiment, NAcore deep brain stimulation reduced responding during a progressive ratio schedule of heroin reinforcement. Finally, deep brain stimulation facilitated extinction from day 1 throughout the course of extinction learning.
Taken together, the differential effects of NAcore and NAshell deep brain stimulation on heroin taking and seeking are in line with the distinct functional roles of these sub-regions therein. Conditioned cues have been shown to be very powerful stimuli for the persistence of addiction and relapse to drug use. Therefore, the present findings that NAcore deep brain stimulation decreases motivation for heroin taking and cue-conditioned behaviour and facilitates extinction learning are very promising, supporting the positive findings from clinical case studies.
深部脑刺激作为一种治疗难治性物质使用依赖的新干预方法正在被探索。伏隔核是一个候选脑区，因为它参与奖赏和动机过程。本研究旨在探讨伏隔核核心区（NAcore）和伏隔核壳区（NAshell）深部脑刺激对大鼠海洛因自我给药模型中海洛因摄取和觅药行为的影响。
在以FR4强化程序进行25或100μg/kg/输注海洛因自我给药期间以及线索和海洛因诱导的复吸期间，施加NAcore和NAshell深部脑刺激。在另一组中，研究了NAcore深部脑刺激对渐进比率程序上海洛因自我给药以及首次消退试验的影响。
NAcore和NAshell深部脑刺激未改变FR4程序上海洛因的自我给药。NAcore深部脑刺激减少了线索诱导而非药物诱导的海洛因觅药行为的复吸，而NAshell深部脑刺激不影响复吸反应。在第二个实验中，NAcore深部脑刺激减少了海洛因强化渐进比率程序期间的反应。最后，深部脑刺激从消退学习过程的第1天起促进了消退。
综上所述，NAcore和NAshell深部脑刺激对海洛因摄取和觅药行为的不同影响与这些亚区域在其中的不同功能作用一致。条件线索已被证明是成瘾持续和复吸药物使用的非常强大的刺激因素。因此，目前NAcore深部脑刺激降低海洛因摄取动机和线索条件行为并促进消退学习的研究结果非常有前景，支持了临床病例研究的阳性结果。
