Methamphetamine-induced dopamine terminal deficits in the nucleus accumbens are exacerbated by reward-associated cues and attenuated by CB1 receptor antagonism.
Methamphetamine-induced dopamine terminal deficits in the nucleus accumbens are exacerbated by reward-associated cues and attenuated by CB1 receptor antagonism.
复制标题
DOI：
10.1016/j.neuropharm.2012.01.013
复制
发表时间：
2012-06
影响因子：
4.7
通讯作者：
Cheer JF
中科院分区：
文献类型：
--
作者：
Loewinger GC;Beckert MV;Tejeda HA;Cheer JF
甲基苯丙胺（METH）暴露主要与对多巴胺能神经元的有害作用有关。虽然有几项研究表明内源性大麻素系统参与了METH的运动、奖励和神经化学效应，但该信号系统在METH对多巴胺末端动力学的影响中的作用尚未阐明。考虑到CB1受体阻滞剂可降低其他精神兴奋剂药物引起的阶段性细胞外多巴胺释放的急性增强作用，并且急性MET诱导的细胞外多巴胺水平升高的程度与多巴胺耗竭的严重程度相关，我们预测，CB1受体拮抗剂利莫那班预处理可降低MET诱导的多巴胺末端改变。此外，我们假设，在奖励相关线索存在的环境中给予METH会增强METH对丘脑核多巴胺释放的急性影响，并加剧多巴胺终末活性的变化。快速扫描循环伏安法被用来测量电诱发的多巴胺释放在脑桥核，并揭示了受损的多巴胺终端完整性的标志物后9天，单剂量的甲基。在存在奖励相关线索的情况下接受METH的动物中，这些症状加重，而在利莫那班预处理的动物中减弱。虽然多巴胺动力学的这些缺陷与仅用METH治疗的动物中METH给药后几天的操作性反应降低有关，但利莫那班预处理的动物表现出与对照相当的操作性反应水平。此外，多巴胺释放与METH给药后几天发生的杠杆按压行为变化显著相关。总之，这些数据表明，内源性大麻素系统参与亚秒多巴胺能反应METH。
Methamphetamine (METH) exposure is primarily associated with deleterious effects to dopaminergic neurons. While several studies have implicated the endocannabinoid system in METH’s locomotor, rewarding and neurochemical effects, a role for this signaling system in METH’s effects on dopamine terminal dynamics has not been elucidated. Given that CB1 receptor blockade reduces the acute potentiation of phasic extracellular dopamine release from other psychomotor stimulant drugs and that the degree of acute METH-induced increases in extracellular dopamine levels is related to the severity of dopamine depletion, we predicted that pretreatment with the CB1 receptor antagonist rimonabant would reduce METH-induced alterations at dopamine terminals. Furthermore, we hypothesized that administration of METH in environments where reward associated-cues were present would potentiate METH’s acute effects on dopamine release in the nucleus accumbens and exacerbate changes in dopamine terminal activity. Fast-scan cyclic voltammetry was used to measure electrically-evoked dopamine release in the nucleus accumbens and revealed markers of compromised dopamine terminal integrity nine days after a single dose of METH. These were exacerbated in animals that received METH in the presence of reward-associated cues, and attenuated in rimonabant-pretreated animals. While these deficits in dopamine dynamics were associated with reduced operant responding on days following METH administration in animals treated with only METH, rimonabant-pretreated animals exhibited levels of operant responding comparable to control. Moreover, dopamine release correlated significantly with changes in lever pressing behavior that occurred on days following METH administration. Together these data suggest that the endocannabinoid system is involved in the subsecond dopaminergic response to METH.
登录
查看更多内容
影响因子：
3.4
作者：
Ago, Yukio;Araki, Ryota;Matsuda, Toshio
通讯作者：
Matsuda, Toshio
影响因子：
15.9
作者：
Alger, Bradley E.;Kim, Jimok
通讯作者：
Kim, Jimok
DOI：
10.1196/annals.1369.021
发表时间：
2006-01-01
期刊：
CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES
影响因子：
--
作者：
Anderson, Karen L.;Itzhak, Yossef
通讯作者：
Itzhak, Yossef
影响因子：
5.3
作者：
Cass, WA;Manning, MW
通讯作者：
Manning, MW
影响因子：
6
作者：
Chang, Linda;Alicata, Daniel;Volkow, Nora
通讯作者：
Volkow, Nora