神经肽三叶因子3对可卡因奖赏效应的影响

目的 探讨神经肽三叶因子3（trefoil factor 3,TFF3）对可卡因诱导的大鼠奖赏行为的影响及其可能机制.方法 50只SD大鼠分为对照组、可卡因组、可卡因＋TFF3（0.01 mg/kg）组、可卡因＋TFF3（0.1 mg/kg）组、可卡因＋TFF3（0.5 mg/kg）组和TFF3（0.1 mg/kg）组六组（n=7～9）,TFF3/生理盐水腹腔注射后30 min后给予可卡因（10 mg/kg）腹腔注射,记录可卡因给药后1h内大鼠自发活动情况.自发活动测试后立即断头取脑,分离伏隔核脑区（n=4～6）,采用高效液相色谱法测定伏隔核脑区神经递质（多巴胺及其代谢物二羟苯乙酸）含量;另有21只大鼠分为对照组和TFF3处理组,经2d生理盐水、可卡因交替训练建立条件位置偏爱（CPP）模型,TFF3（0.1 mg/kg）/生理盐水腹腔注射后30 min后给予可卡因（5 mg/kg）腹腔注射TFF3,观察其对可卡因CPP评分的影响.结果 腹腔注射TFF3（0.1 mg/kg）可增强可卡因诱导的奖赏行为,表现为TFF3显著增加可卡因诱导的大鼠自发活性变化对照组、可卡因组、可卡因＋TFF3（0.01 mg/kg）和TFF3（0.1 mg/kg）组大鼠1h内运动总路程分别为：（180±41）cm,（359±53）cm,（590±75）cm,（153±27）cm];条件性位置偏爱实验显示,TFF3（0.1 mg/kg）能显著增强可卡因诱导的条件性位置偏爱的形成训练后偏爱值分别为：（98±18）s,（187±24）s];高效液相色谱分析发现,TFF3能显著增加由可卡因诱导的大鼠伏隔核多巴胺变化对照组、可卡因组、可卡因＋TFF3（0.1 mg/kg）和TFF3（0.1 mg/kg）组分别为：（0.65±0.1）ng/ml,（1.24±0.14）ng/ml,（1.75±0.23） ng/ml,（0.74±0.21） ng/ml].结论 神经肽TFF3能够调节可卡因诱导的奖赏行为,这种调节作用可能与其影响伏隔核脑区多巴胺含量调节有关.

Neuropeptide trefoil factor 3 increases reward effects of cocaine in rats

Objective To investigate the role of neuropeptide trefoil factor 3 （TFF3） in cocaine reward responses and the underlying mechanism.Methods Fifty SD rats were divided into 6 groups including Control group,Cocaine group,Cocaine ＋ TFF3 （0.01 mg/kg） group,cocaine ＋ TFF3 （0.1 mg/kg） group,cocaine ＋ TFF3 （0.5 mg/kg） group and TFF3 （0.1 mg/kg） group,ip,n=7 ～ 9）,and were treated with TFF3 / saline （ip）,30 min later,rats were injected with cocaine （10 mg/kg ip） followed by 1 h hypedocomotion test.Immediately after behavioral test,rats （n=4～6） were decapitated and tissues of nucleus accumbens （NAc） were isolated and prepared for neurotransmitters analysis by HPLC; Another twenty one rats were divided into control and TFF3-treatment group,and the rats were trained with a modified 2-day cocaine CPP conditioning procedure.During cocaine CPP conditioning process,saline or TFF3 （0.1 mg/kg ip） was injected 30 min prior to cocaine injection （5 mg/kg ip）.Results Systemic administration of TFF3 （0.1 mg/kg,ip） significantly increased the cocaine-induced locomotor activity （Total distance in 1 hour were （180±41） cm,（359±53） cm,（590±75） cm,（153±27） cm for Control,Vehicle ＋ Cocaine,TFF3＋Cocaine and TFF3＋Vehicle groups respectively） and augmented cocaine rewarding effects in CPP（Post-training CPP score were （98± 18） s,（187±24） s for Vehicle ＋ Cocaine,TFF3＋Cocaine groups respectively）.TFF3 （0.1 mg/kg ip） administration increased the dopamine concentration in the NAc induced by cocaine injection （（0.65±0.1） ng/ml,（1.24±0.14） ng/ml,（1.75±0.23） ng/ml,（0.74±0.21） ng/ml for Control,Cocaine,TFF3 ＋ Cocaine and TFF3 ＋ Vehicle groups respectively）.Conclusion TFF3 is involved in regulation of behavioral response to cocaine,which is associated with the increasing of dopamine in the NAc.