Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence.
Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence.
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DOI：
10.1111/adb.13241
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发表时间：
2022-11
影响因子：
3.4
通讯作者：
España RA
中科院分区：
文献类型：
--
作者：
Samson KR;Xu W;Kortagere S;España RA
治疗阿片类药物使用障碍的一个主要障碍是在戒断期间持续寻求药物或渴望药物，这被认为会导致复发。中脑边缘通路中的多巴胺神经传递被认为有助于阿片类药物的强化，但多巴胺影响药物寻求的过程尚未阐明。为了检查戒断期间寻求阿片类药物是否与多巴胺神经传递的改变相关，雌性和雄性大鼠在间歇性强化方案下自行施用羟考酮。自我给药后，大鼠经历强制禁欲期，并进行提示诱导寻找测试以评估羟考酮寻求。最终寻找测试后一天，处死大鼠以在伏隔核中进行离体快速扫描循环伏安法和蛋白质印迹法。与未接受羟考酮的大鼠相比，大鼠在禁欲第 2 天和第 15 天表现出多巴胺摄取率降低。此外，在禁欲第 15 天，大鼠的多巴胺转运蛋白磷酸化降低。此外，在未使用羟考酮的大鼠和羟考酮戒断期间、戒断第 2 天和戒断第 15 天的大鼠中，伏核局部应用羟考酮可降低多巴胺摄取率。这些观察结果表明，羟考酮戒断会导致多巴胺传输功能障碍，这可能有助于戒断期间持续寻求羟考酮。间歇性使用羟考酮降低了禁欲第 2 天和第 15 天伏隔核核心的多巴胺摄取率。此外，对伏隔核核心急性应用羟考酮导致多巴胺摄取率大幅降低。
A major obstacle in treating opioid use disorder is the persistence of drug seeking or craving during periods of abstinence, which is believed to contribute to relapse. Dopamine neurotransmission in the mesolimbic pathway is posited to contribute to opioid reinforcement, but the processes by which dopamine influences drug seeking have not been elucidated. To examine whether opioid seeking during abstinence is associated with alterations in dopamine neurotransmission, female and male rats self-administered oxycodone under an intermittent access schedule of reinforcement. Following self-administration, rats underwent a forced abstinence period and cue-induced seeking tests were conducted to assess oxycodone seeking. One day following the final seeking test, rats were sacrificed to perform ex vivo fast scan cyclic voltammetry and western blotting in the nucleus accumbens. Rats displayed reduced dopamine uptake rate on abstinence day 2 and abstinence day 15, compared to oxycodone-naïve rats. Further, on abstinence day 15 rats had reduced phosphorylation of the dopamine transporter. Additionally, local application of oxycodone to the nucleus accumbens reduced dopamine uptake rate in oxycodone-naïve rats and in rats during oxycodone abstinence, on abstinence day 2 and abstinence day 15. These observations suggest that abstinence from oxycodone results in dysfunctional dopamine transmission, which may contribute to sustained oxycodone seeking during abstinence. Intermittent access to oxycodone reduced dopamine uptake rate in the nucleus accumbens core on abstinence day 2 and day 15. Additionally, acute application of oxycodone to the nucleus accumbens core induced a robust reduction in dopamine uptake rate.
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DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
3.3
作者：
Blackwood, Christopher A.;Leary, Michael;Cadet, Jean Lud
通讯作者：
Cadet, Jean Lud
影响因子：
3.6
作者：
DWORKIN, SI;GUERIN, GF;SMITH, JE
通讯作者：
SMITH, JE
影响因子：
4.3
作者：
Blackwood, Christopher A.;McCoy, Michael T.;Cadet, Jean Lud
通讯作者：
Cadet, Jean Lud
影响因子：
7.3
作者：
通讯作者：
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