Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA.
Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA.
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DOI：
10.1007/s00213-011-2266-8
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发表时间：
2011-11
影响因子：
3.4
通讯作者：
Miczek, Klaus A.
中科院分区：
文献类型：
--
作者：
Boyson, Christopher O.;Miguel, Tarciso T.;Quadros, Isabel M.;DeBold, Joseph F.;Miczek, Klaus A.
间歇性地暴露在社会失败压力下可以诱导长期的神经可塑性，这可能会影响不断升级的可卡因服用行为。应激性接触可导致腹侧被盖区(VTA)多巴胺神经元的激活，该神经元受促肾上腺皮质激素释放因子(CRF)神经元的调节。本研究旨在通过使用CRF受体亚型1(CRF-R1)拮抗剂来预防间歇性、短暂的社会失败应激对随后静脉注射(IV)可卡因自身给药的影响。Long-Evans大鼠在10天内经历了4次间歇性的社会失败经历，间隔72小时。两个实验检测了CRF-R1亚型在应激期间对运动敏化和可卡因自身给药的后期表达的全身或VTA拮抗作用。在固定(0.75 mg/kg/次)和递增比率强化(0.3 mg/kg/次)期间，包括连续24小时的“狂欢”(0.3 mg/kg/次)。预先给予CRF-R1拮抗剂CP 154,526(20 mg/kg ip)。在每个社会失败事件之前，防止应激诱导的运动对可卡因挑战的敏感化发展，并防止在24小时的“狂欢”期间升级的可卡因自我给药。此外，在每个社会失败事件之前，向VTA中预先注入促肾上腺皮质激素释放因子-1拮抗剂(0.3μg/0.5μL/侧)，防止应激诱导的运动对可卡因挑战的敏化，并防止在24小时的“狂欢”中升级的可卡因自我给药。目前的结果表明，VTA中CRF-R1亚型在应激诱导的运动敏感化的发展中起关键作用，这种敏感化可能有助于在24小时的“狂欢”中不断获得可卡因自我给药的升级。
Intermittent exposure to social defeat stress can induce long-term neural plasticity that may influence escalated cocaine-taking behavior. Stressful encounters can lead to activation of dopamine neurons in the ventral tegmental area (VTA), which are modulated by corticotropin releasing factor (CRF) neurons. The study aims to prevent the effects of intermittently scheduled, brief social defeat stress on subsequent intravenous (IV) cocaine self-administration by pretreatment with a CRF receptor subtype 1 (CRF-R1) antagonist. Long–Evans rats were submitted to four intermittent social defeat experiences separated by 72 h over 10 days. Two experiments examined systemic or intra-VTA antagonism of CRF-R1 subtype during stress on the later expression of locomotor sensitization and cocaine self-administration during fixed (0.75 mg/kg/infusion) and progressive ratio schedules of reinforcement (0.3 mg/kg/infusion), including a continuous 24-h “binge” (0.3 mg/kg/infusion). Pretreatment with a CRF-R1 antagonist, CP 154,526, (20 mg/kg i.p.) prior to each social defeat episode prevented the development of stress-induced locomotor sensitization to a cocaine challenge and prevented escalated cocaine self-administration during a 24-h “binge” In addition, pretreatment with a CRF-R1 antagonist (0.3 μg/0.5 μl/side) into the VTA prior to each social defeat episode prevented stress-induced locomotor sensitization to a cocaine challenge and prevented escalated cocaine self-administration during a 24-h “binge”. The current results suggest that CRF-R1 subtype in the VTA is critically involved in the development of stress-induced locomotor sensitization which may contribute to escalated cocaine self-administration during continuous access in a 24-h “binge”.
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