Post-retrieval disruption of a cocaine conditioned place preference by systemic and intrabasolateral amygdala β2- and α1-adrenergic antagonists
Post-retrieval disruption of a cocaine conditioned place preference by systemic and intrabasolateral amygdala β2- and α1-adrenergic antagonists
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DOI：
10.1101/lm.1648509
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发表时间：
2009-12-01
影响因子：
2
通讯作者：
Lattal, K. Matthew
中科院分区：
文献类型：
--
作者：
Bernardi, Rick E.;Ryabinin, Andrey E.;Lattal, K. Matthew
先前的工作已经证明了联想学习范式的检索后损伤，包括使用非特异性β-肾上腺素能受体（β-AR）拮抗剂由滥用药物介导的联想学习范式。对于特定 β-AR 亚型或其他肾上腺素能受体在这些效应中的作用，人们知之甚少。当前的研究检查了可卡因条件性位置偏好（CPP）恢复后β（1）和β（2）以及α（1）肾上腺素受体拮抗作用的影响。我们发现，在无药 CPP 测试后给予 β(2) 拮抗剂 ICI 118,551（8 mg/kg 腹膜内 [IP]）或 α(1) 拮抗剂哌唑嗪（1 mg/kg IP）的大鼠在随后的测试中表现出减弱的偏好，而 β(1) 拮抗剂倍他洛尔（5 或 10 mg/kg IP）和较低剂量的哌唑嗪（0.3 mg/kg IP）则没有表现出偏好。效果。此外，测试后将ICI 118,551（6 nmol/侧）或哌唑嗪（0.5 nmol/侧）微量输注至基底外侧杏仁核（BLA）也会损害随后的偏好。在没有偏好测试的情况下，对家中笼中的大鼠进行全身或 BLA 内 ICI 118,551 或哌唑嗪给药，24 小时后对 CPP 没有影响。 ICI 118,551 还减弱了 CPP 测试诱导的 BLA 中的 FOS 反应。这些结果首次证明了 α(1) 和 β(2) 特异性肾上腺素能机制在检索后记忆过程中的作用。这些全身和位点特异性注射以及 FOS 免疫组织化学分析表明 BLA 内特定去甲肾上腺素信号传导机制在修复后可塑性中的重要性。
Previous work has demonstrated post-retrieval impairment in associative learning paradigms, including those mediated by drugs of abuse, using nonspecific beta-adrenergic receptor (beta-AR) antagonists. Remarkably little is known about the role of the specific beta-AR subtypes, or other adrenergic receptors, in these effects. The current study examined the effects of beta(1) and beta(2), as well as alpha(1)-adrenergic receptor antagonism following retrieval of a cocaine conditioned place preference (CPP). We found that rats administered the beta(2) antagonist ICI 118,551 (8 mg/kg intraperitoneal [IP]) or the alpha(1) antagonist prazosin (1 mg/kg IP) following a drug-free test for CPP showed attenuated preference during a subsequent test, while the beta(1) antagonist betaxolol (5 or 10 mg/kg IP) and a lower dose of prazosin (0.3 mg/kg IP) had no effect. Furthermore, post-test microinfusion of ICI 118,551 (6 nmol/side) or prazosin (0.5 nmol/side) into the basolateral amygdala (BLA) also impaired a subsequent preference. Systemic or intra-BLA ICI 118,551 or prazosin administered to rats in their home cages, in the absence of a preference test, had no effect on CPP 24 h later. ICI 118,551 also attenuated the FOS response in the BLA induced by the CPP test. These results are the first to demonstrate a role for alpha(1)- and beta(2)-specific adrenergic mechanisms in post-retrieval memory processes. These systemic and site-specific injections, as well as the FOS immunohistochemical analyses, implicate the importance of specific noradrenergic signaling mechanisms within the BLA in post-retrieval plasticity.