Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.
Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.
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DOI：
10.3389/fphar.2023.1199655
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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导言：阿片类药物是美国过量死亡的主要原因，在2020年造成近7万人死亡。脑深部电刺激（DBS）是一种治疗药物使用障碍的新方法。在这里，我们假设VTA DBS可以调节氧可酮的多巴胺能和呼吸作用。方法：采用多循环方波伏安法（M-CSWV）研究深度脑刺激（130 Hz, 0.2 ms, 0.2 mA）对多巴胺能神经元丰富的鼠腹节区（VTA）的影响，探讨羟考酮（2.5 mg/kg, i.v.）对氨基甲酸乙酯麻醉大鼠（1.5 g/kg, i.p）伏隔核（NAcc）强直性胞外多巴胺水平和呼吸频率的影响。结果：与基线（150.7±15.5 nM）和生理盐水（152.0±16.1 nM）相比，静脉注射羟考酮导致NAcc强直性多巴胺水平（296.9±37.0 nM）升高（150.7±15.5 nM比296.9±37.0 nM, p = 0.022, n = 5）。羟考酮诱导的NAcc多巴胺浓度显著升高与呼吸速率急剧降低相关（111.7±2.6 min - 1 vs 67.9±8.3 min - 1；羟考酮前vs后；p < 0.001）。针对VTA的持续DBS （n = 5）降低了基线多巴胺水平，将氧可酮诱导的多巴胺水平升高降低至（+39.0% vs +95%），并抑制呼吸（121.5±6.7 min−1 vs 105.2±4.1 min−1；氧可酮前vs后；p = 0.072）。讨论：在这里，我们证明了VTA DBS减轻了羟考酮诱导的NAcc多巴胺水平的增加，并逆转了呼吸抑制。这些结果支持了使用神经调节技术治疗药物成瘾的可能性。
Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone. Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.). Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min−1 vs. 67.9 ± 8.3 min−1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min−1 vs. 105.2 ± 4.1 min−1; pre- vs. post-oxycodone; p = 0.072). Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.
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影响因子：
4.1
作者：
Chang, Su-Youne;Kimble, Christopher J.;Lee, Kendall H.
通讯作者：
Lee, Kendall H.
影响因子：
9.9
作者：
Akram, Harith;Miller, Sarah;Zrinzo, Ludvic
通讯作者：
Zrinzo, Ludvic
影响因子：
3
作者：
Bass CE;Grinevich VP;Gioia D;Day-Brown JD;Bonin KD;Stuber GD;Weiner JL;Budygin EA
通讯作者：
Budygin EA
影响因子：
48
作者：
Clark, Jeremy J.;Sandberg, Stefan G.;Wanat, Matthew J.;Gan, Jerylin O.;Horne, Eric A.;Hart, Andrew S.;Akers, Christina A.;Parker, Jones G.;Willuhn, Ingo;Martinez, Vicente;Evans, Scott B.;Stella, Nephi;Phillips, Paul E. M.
通讯作者：
Phillips, Paul E. M.
影响因子：
--
作者：
BURGESS, ML;DAVIS, JM;BUGGY, J
通讯作者：
BUGGY, J