Knockdown of corticotropin-releasing factor 1 receptors in the ventral tegmental area enhances conditioned fear

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• 作者：Nicola A. Chen^a ; ^b ; Despina E. Ganella^a ; ^b ; Ross A.D. Bathgate^a ; ^b ; ^c ; Alon Chen^d ; Andrew J. Lawrence^a ; ^b ; Jee Hyun Kim^a ; ^b ; ^{drjeehyunkim@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Stress ; Fear ; VTA ; CRF ; Memory
• 刊名：European Neuropsychopharmacology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：26
• 期：9
• 页码：1533-1540
• 全文大小：1363 K

文摘

The neuropeptide corticotropin-releasing factor (CRF) coordinates the physiological and behavioural responses to stress. CRF receptors are highly expressed in the ventral tegmental area (VTA), an important region for motivated behaviour. Therefore, we examined the role of CRF receptor type 1 (CRFR1) in the VTA in conditioned fear, using a viral-mediated RNA interference approach. Following stereotaxic injection of a lentivirus that contained either shCRF-R1 or a control sequence, mice received tone-footshock pairings. Intra-VTA shCRF-R1 did not affect tone-elicited freezing during conditioning. Once conditioned fear was acquired, however, shCRF-R1 mice consistently showed stronger freezing to the tone even after extinction and reinstatement. These results implicate a novel role of VTA CRF-R1 in conditioned fear, and suggest how stress may modulate aversive learning and memory.