Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats.
Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats.
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DOI：
10.1523/jneurosci.0637-11.2011
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发表时间：
2011-07-06
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影响因子：
--
通讯作者：
Covington HE 3rd
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文献类型：
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作者：
Miczek KA;Nikulina EM;Shimamoto A;Covington HE 3rd
表面上令人厌恶的压力体验和强烈奖励的药物服用之间的神经联系仍然有待描述。流行病学数据将压力与各种药物的滥用联系起来，实验数据确定了决定偶发性社会压力如何加剧可卡因动机和可卡因实际自我给药的条件。两种类型的社会压力一直是实验研究的重点，在Long-Evans大鼠，因为它们产生不同的变化，药物或糖奖励的行为和神经适应。情景性社交失败压力包括实验大鼠和Long-Evans品系的侵略性居民大鼠之间在10天内的四次短暂对抗。从属压力包括连续五周暴露于一个有攻击性的居民，同时生活在居民家中的保护笼中，每天都有短暂的对抗。这些应激经历导致1）在固定比率时间表下增加静脉内可卡因自我给药，在间歇性击败的入侵大鼠中延长暴食样访问，但抑制连续从属大鼠的可卡因摄入; 2）在从属大鼠中恶化的糖偏好和摄入以及减少的探索行为，但不是间歇性击败的大鼠; 3）在n.通过在体内微透析和增加被盖BDNF的episodically失败的大鼠，而连续从属大鼠表现出抑制DA和BDNF的反应。这些不同的神经适应社会压力可能代表可卡因“暴食”相对于快感缺乏样恶化的奖励过程中的从属压力的加剧基板。
The neural link between ostensibly aversive stress experiences and intensely rewarding drug taking remains to be delineated. Epidemiological data associate stress and the abuse of various drugs, and experimental data identify the conditions that determine how episodic social stress intensifies the motivation for cocaine and the actual self-administration of cocaine. Two types of social stress have been the focus of experimental study in Long-Evans rats, since they engender divergent changes in drug- or sugar-rewarded behavior and in neuroadaptation. Episodic social defeat stress consists of four brief confrontations between the experimental rat and an aggressive resident rat of the Long-Evans strain over the course of 10 days. Subordination stress involves the continuous exposure to an aggressive resident for five weeks, while living in a protective cage within the resident’s home cage with brief daily confrontations. These stress experiences result in 1) increased intravenous cocaine self-administration under a fixed ratio schedule with prolonged binge-like access in episodically defeated intruder rats, but suppressed cocaine intake by continuously subordinate rats; 2) deteriorated sugar preference and intake and decreased exploratory behavior in subordinate, but not intermittently defeated, rats; 3) a sensitized dopamine (DA) response in the n. accumbens via in vivo microdialysis and increased tegmental BDNF in episodically defeated rats, whereas the continuously subordinate rats show suppression of the DA and BDNF responses. These divergent neuroadaptations to social stress may represent the substrates for the intensification of cocaine “bingeing” relative to the anhedonia-like deterioration of reward processes during subordination stress.