Prazosin during fear conditioning facilitates subsequent extinction in male C57Bl/6N mice.
Prazosin during fear conditioning facilitates subsequent extinction in male C57Bl/6N mice.
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DOI：
10.1007/s00213-018-5001-x
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发表时间：
2019-01
影响因子：
3.4
通讯作者：
Clem RL
中科院分区：
文献类型：
--
作者：
Lucas EK;Wu WC;Roman-Ortiz C;Clem RL
Recovery from a traumatic experience requires extinction of cue-based fear responses, a process that is impaired in post-traumatic stress disorder. While studies suggest a link between fear behavioral flexibility and noradrenaline signaling, the role of specific receptors and brain regions in these effects is unclear. Here we examine the role of prazosin, an α1-adrenergic receptor (α1-AR) antagonist, in auditory fear conditioning and extinction. C57Bl/6N mice were subjected to auditory fear conditioning and extinction in combination with systemic (0.1-2 mg/kg) or local microinjections (3 or 6 mM) of the α1-AR antagonist prazosin into the prelimbic division of medial prefrontal cortex or basolateral amygdala. Conditioned fear and anxiety-like behaviors were compared with vehicle-injected control animals. Mice that received systemic prazosin prior to fear conditioning exhibited similar initial levels of cue-elicited freezing compared to vehicle controls on the following day. However, at all doses tested fear that was acquired during prazosin treatment was more readily extinguished, whereas anxiety-like behavior on the day of extinction was unaffected. A similar pattern of results was observed when prazosin was microinjected into the basolateral amygdala but not the prelimbic cortex. In contrast to pre-conditioning injections, prazosin administration prior to extinction had no effect on freezing. Our results indicate that α1-AR activity during aversive conditioning is dispensable for memory acquisition, but renders conditioned fear more impervious to extinction. This suggests that behavioral flexibility is constrained by noradrenaline at the time of initial learning via activation of a specific AR isoform.
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DOI：
10.1101/lm.045898.117
发表时间：
2017-11
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
--
作者：
Homan P;Lin Q;Murrough JW;Soleimani L;Bach DR;Clem RL;Schiller D
通讯作者：
Schiller D
影响因子：
5.6
作者：
Lin, Chen-Cheng;Tung, Che-Se;Liu, Yia-Ping
通讯作者：
Liu, Yia-Ping
影响因子：
7.6
作者：
Giustino, Thomas F.;Seemann, Jocelyn R.;Maren, Stephen
通讯作者：
Maren, Stephen
影响因子：
3.3
作者：
Luo, F.;Tang, H.;Cheng, Z. -Y.
通讯作者：
Cheng, Z. -Y.
影响因子：
2
作者：
Lazzaro, Stephanie C.;Hou, Mian;Cain, Christopher K.
通讯作者：
Cain, Christopher K.