Involvement of noradrenergic neurotransmission in the stress- but not cocaine-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: role for β-2 adrenergic receptors.
Involvement of noradrenergic neurotransmission in the stress- but not cocaine-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: role for β-2 adrenergic receptors.
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DOI：
10.1038/npp.2010.86
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发表时间：
2010-10
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影响因子：
--
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中枢去甲肾上腺素能系统对压力源和可卡因的反应使去甲肾上腺素成为一种潜在的共同机制，通过该机制，药物重新暴露和压力刺激促进复发。本研究调查了去甲肾上腺素能系统在雄性 C57BL/6 小鼠中通过可卡因和压力恢复可卡因诱导的条件性位置偏爱的作用。可卡因（15 mg/kg，腹腔注射）诱导的条件性位置偏好通过在没有药物的情况下重复暴露于该装置而被消除，并通过可卡因挑战（15 mg/kg）、暴露于压力源（6分钟强迫游泳；FS；20–25°C水）或施用α-2肾上腺素受体（AR）拮抗剂育亨宾（2 mg/kg，腹腔注射）或给药重新建立BRL44408（5、10 毫克/千克，腹膜内注射）。为了研究 AR 的作用，在恢复测试之前，小鼠接受非选择性 β AR 拮抗剂普萘洛尔（5、10 mg/kg，腹腔注射）、α-1 AR 拮抗剂哌唑嗪（1、2 mg/kg，腹腔注射）或 α-2 AR 激动剂可乐定（0.03、0.3 mg/kg，腹腔注射）。可乐定、哌唑嗪和普萘洛尔未能阻止可卡因诱导的恢复。低剂量（0.03 mg/kg）但不高剂量（0.3 mg/kg）可乐定完全阻断 FS 诱导的恢复，但不能阻断育亨宾的恢复。普萘洛尔（但不是哌唑嗪）可阻止育亨宾和 FS 的恢复，表明β AR 参与其中。 β-2 AR 拮抗剂 ICI-118551（1 mg/kg，腹膜内）也能阻断 FS 诱导的恢复，但 β-1 AR 拮抗剂倍他洛尔（10 mg/kg，腹膜内）则不然。这些发现表明，压力诱导的恢复需要通过 β2 AR 的去甲肾上腺素能信号传导，而可卡因诱导的恢复不需要 AR 激活，尽管刺激中枢去甲肾上腺素能神经传递足以恢复。
The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, ip) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and re-established by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim; FS; 20–25°C water), or administration of the alpha-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, ip) or BRL44408 (5, 10 mg/kg, ip). To investigate the role of ARs, mice received the non-selective beta AR antagonist, propranolol (5, 10 mg/kg, ip), the alpha-1 AR antagonist, prazosin (1, 2 mg/kg, ip), or the alpha-2 AR agonist, clonidine (0.03, 0.3 mg/kg, ip) prior to reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting involvement of beta ARs. The beta-2 AR antagonist ICI-118551 (1 mg/kg, ip), but not the beta-1 AR antagonist, betaxolol (10 mg/kg, ip) also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through beta-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate.
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影响因子：
2.7
作者：
Feltenstein, Matthew W.;See, Ronald E.
通讯作者：
See, Ronald E.
DOI：
10.1196/annals.1369.039
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：
Jimenez-Rivera, Carlos A.;Feliu-Mojer, Monica;Vazquez-Torres, Rafael
通讯作者：
Vazquez-Torres, Rafael
影响因子：
5.3
作者：
Erb, S;Shaham, Y;Stewart, J
通讯作者：
Stewart, J
影响因子：
3.3
作者：
FINLAY, JM;ZIGMOND, MJ;ABERCROMBIE, ED
通讯作者：
ABERCROMBIE, ED
影响因子：
3.4
作者：
HARRIS, GC;ASTONJONES, G
通讯作者：
ASTONJONES, G