Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats.
Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats.
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DOI：
10.1523/jneurosci.5277-07.2008
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发表时间：
2008-08-27
期刊：
影响因子：
--
通讯作者：
Pierce RC
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文献类型：
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作者：
Vassoler FM;Schmidt HD;Gerard ME;Famous KR;Ciraulo DA;Kornetsky C;Knapp CM;Pierce RC
越来越多的证据表明，脑深部电刺激（DBS）目前被用作神经系统疾病的治疗方法，也可能有效治疗精神疾病。在这里，我们研究了DBS的核壳可卡因引发诱导的药物寻求，复发的动物模型的恢复的影响。允许大鼠自我施用可卡因（0.25mg，i. v.）每天2小时，持续21天，然后通过用盐水代替可卡因来熄灭可卡因寻求行为。在恢复阶段，通过双极不锈钢电极向双侧髓核壳给予DBS。以160 Hz的频率和150 μ A的电流强度递送双相对称脉冲。DBS在可卡因（0、5、10或20 mg/kg，i. p.）并在每个2小时的恢复期内持续进行。结果表明，只有较高剂量的可卡因（10和20毫克/公斤）产生强大的和可靠的恢复可卡因寻求。DBS的核壳显着衰减这些较高的可卡因剂量沉淀的药物寻求的恢复。另外的实验表明，这种DBS效应在解剖学上和肿瘤特异性上都是如此。因此，背侧纹状体的DBS对可卡因的恢复没有影响，背侧纹状体的DBS对寻找食物的恢复没有影响。综上所述，这些结果表明，DBS的髓核壳可能是一个潜在的治疗选择，在治疗严重的可卡因成瘾。
Increasing evidence suggests that deep brain stimulation (DBS), which is currently being used as a therapy for neurological diseases, may be effective in the treatment of psychiatric disorders as well. Here, we examined the influence of DBS of the nucleus accumbens shell on cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.25 mg, i.v.) 2 hours daily for 21 days and then cocaine seeking behavior was extinguished by replacing cocaine with saline. During the reinstatement phase, DBS was administered bilaterally to the nucleus accumbens shell through bipolar stainless steel electrodes. Biphasic symmetrical pulses were delivered at a frequency of 160 Hz and a current intensity of 150 μAmps. DBS began immediately after a priming injection of cocaine (0, 5, 10 or 20 mg/kg, i.p.) and continued throughout each 2-hour reinstatement session. Results indicated that only the higher doses of cocaine (10 and 20 mg/kg) produced robust and reliable reinstatement of cocaine seeking. DBS of the nucleus accumbens shell significantly attenuated the reinstatement of drug seeking precipitated by these higher cocaine doses. Additional experiments indicated that this DBS effect was both anatomically and reinforcer-specific. Thus, DBS of the dorsal striatum had no influence on cocaine reinstatement and DBS of the accumbens shell did not affect the reinstatement of food seeking. Taken together, these results suggest that DBS of the nucleus accumbens shell may be a potential therapeutic option in the treatment of severe cocaine addiction.