Stressor controllability modulates stress-induced dopamine and serotonin efflux and morphine-induced serotonin efflux in the medial prefrontal cortex
Stressor controllability modulates stress-induced dopamine and serotonin efflux and morphine-induced serotonin efflux in the medial prefrontal cortex
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DOI：
10.1038/sj.npp.1300206
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发表时间：
2003-09-01
影响因子：
7.6
通讯作者：
Maier, SF
中科院分区：
文献类型：
--
作者：
Bland, ST;Hargrave, D;Maier, SF
以前已经表明，不可避免的（IS），但不能逃避（ES）的压力加强吗啡的奖励特性，如测量的条件性位置偏好和心理激活，这种增强作用可能是由中缝背核（DRN）5-羟色胺（5-HT）神经元介导的。内侧前额叶皮层（mPFC）与奖赏和压力有关，是DRN的投射区域。mPFC还包含来自腹侧被盖区的多巴胺能传入，这一直是许多研究的焦点，探索药物的奖励特性和压力的厌恶特性。mPFC在应激/药物反应性相互作用中的作用在很大程度上是未知的。本研究采用在体微透析技术，观察了大鼠前额叶皮质（mPFC）在应激（IS）、应激（ES）和非应激（NS）时5-HT和多巴胺（DA）的流出。IS和ES大鼠接受的压力在轭对。应激源由尾电击组成，ES大鼠可以终止这两种大鼠。IS期间观察到5-HT和DA水平大幅增加，但ES或NS期间则未观察到。DA和5-HT流出也测量24小时后在相同的大鼠在响应吗啡（3毫克/公斤）或生理盐水。持续增加5-羟色胺水平后，观察到吗啡在大鼠先前收到IS，但没有在大鼠已收到ES或NS。吗啡给药后DA外排无明显变化。因此，5-HT和DA在mPFC可能参与应激可控性的影响，和5-HT神经元的敏感性IS延伸到mPFC和吗啡作为一个挑战。
It has previously been shown that inescapable ( IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress. The role of the mPFC in stress/drug reactivity interactions is largely unknown. The present study used in vivo microdialysis to examine 5-HT and dopamine (DA) efflux in the mPFC of rats during IS, ES or no stress (NS). IS and ES rats received the stressor in yoked pairs. The stressor consisted of tailshocks that could be terminated for both rats by the ES rats. Large increases in 5-HT and DA levels were observed during IS but not ES or NS. DA and 5-HT efflux were also measured 24 h later in the same rats in response to morphine (3 mg/kg) or saline. Sustained increases in 5-HT levels were observed after morphine in rats that had previously received IS but not in rats that had received ES or NS. No changes in DA efflux were observed after morphine. Thus, 5-HT and DA in the mPFC may be involved in stressor controllability effects, and the sensitization of 5-HT neurons by IS extends to the mPFC and to morphine as a challenge.