Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity.
Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity.
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发表时间：
1983-10
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通讯作者：
P. Kalivas;David J. Stanley;Erik Widerlöv;G. Breese;A. Prange
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作者：
P. Kalivas;David J. Stanley;Erik Widerlöv;G. Breese;A. Prange
脑啡肽已被免疫组织化学鉴定为存在于腹侧被盖区中边缘多巴胺能核周围和伏隔核轴突终末附近。为了探讨内源性脑啡肽对中脑边缘多巴胺（DA）系统的生理调节作用，研究了脑啡肽类似物d - ala2 - met5 -脑啡肽酰胺（DALA）在脑腹侧被盖区和伏隔核的微注射效果。通过运动和饲养行为以及DA及其代谢物在中脑边缘终末区的浓度变化来评价中脑边缘多巴胺能功能。腹侧被盖区微量注射DALA可使运动和饲养能力呈剂量依赖性增加，这种增加可被伏隔核的抗精神病药所拮抗。由于将DALA注入腹侧被盖与向伏隔核注入阈下剂量的DA相结合，并产生3,4-二羟基苯乙酸和3,4-二羟基苯乙酸/DA比值的剂量相关增加，这些数据与DALA治疗激活中脑边缘DA系统的假设一致。在伏隔核内注射DALA也能引起运动和饲养能力的剂量依赖性增加。然而，这种行为效应被证明是独立于中脑边缘DA系统的，因为无论是向伏隔核注射抗精神病药，还是用6-羟多巴胺破坏中脑边缘DA系统，都不能阻断这种治疗产生的行为反应。此外，在注射后15、30和60分钟，DALA注射到伏隔核并没有改变伏隔核DA及其代谢物的水平。（摘要删节250字）
Enkephalin has been identified by immunohistochemistry to be present in the vicinity of mesolimbic dopaminergic perikarya in the ventral tegmental area and axonal terminals in the nucleus accumbens. To evaluate the possibility that endogenous enkephalin may physiologically modulate the mesolimbic dopamine (DA) system, the effect of microinjection of the peptidase-resistant enkephalin analog, D-Ala2-Met5-enkephalinamide (DALA), in the ventral tegmental area and nucleus accumbens was examined. Locomotion and rearing behavior and alteration in concentration of DA and its metabolites in mesolimbic terminal areas were used to evaluate mesolimbic dopaminergic function. Microinjection of DALA into the ventral tegmental area produced a dose-dependent increase in locomotion and rearing which was antagonized by neuroleptic administration in the nucleus accumbens. Inasmuch as DALA administration into the ventral tegmentum was additive with a subthreshold dose of DA injected into the nucleus accumbens and produced a dose-related increase in 3,4-dihydroxyphenylacetic acid and the 3,4-dihydroxyphenylacetic acid/DA ratio, these data are consistent with the postulate that this treatment with DALA activates the mesolimbic DA system. DALA microinjection into the nucleus accumbens also produced a dose-dependent increase in locomotion and rearing. However, this behavioral effect was shown to be independent of the mesolimbic DA system because neither neuroleptic injection into the nucleus accumbens nor destruction of the mesolimbic DA system with 6-hydroxydopamine blocked the behavioral response produced by this treatment. Furthermore, DALA injection into the nucleus accumbens did not alter nucleus accumbens levels of DA or its metabolites at 15, 30 or 60 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)