L-tryptophan attenuation of the dopaminergic and behavioral responses to cocaine.
L-tryptophan attenuation of the dopaminergic and behavioral responses to cocaine.
复制标题
L-色氨酸减弱可卡因的多巴胺能和行为反应。
DOI：
10.1016/s0024-3205(01)01276-0
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发表时间：
2001
期刊：
影响因子：
6.1
通讯作者：
Abumrad,NN
中科院分区：
文献类型：
--
作者：
Molina,PE;Ahmed,N;Gatley,J;Volkow,ND;Abumrad,NN
本研究评估了急性静脉注射l -色氨酸（血清素的中性氨基酸前体）对可卡因诱导的多巴胺能反应的影响。在研究前5天，雄性sd大鼠在伏隔核植入引导管，并在研究前一天植入血管导管（颈动脉和颈静脉）。用微透析法测定自由活动大鼠伏隔核胞外多巴胺水平。在2小时的平衡期后，动物被随机分配（每组n= 7-8），接受持续静脉输注l -色氨酸（200 mg/kg/h）或等量（2 ml/h）生理盐水。注射90分钟后，腹腔注射可卡因（20 mg/kg）。可卡因增加伏隔核微透析物多巴胺水平（30分钟500%）。这与明显的多动症有关。色氨酸输注使血浆色氨酸升高（8倍），并使可卡因引起的伏隔核微透析多巴胺水平升高钝化约60%。此外，色氨酸减弱了可卡因引起的运动活动。色氨酸的这些神经化学和行为效应与脑组织血清素含量的显著增加有关。这些研究的结果证明了急性饮食操纵可卡因神经化学和行为反应的可行性。对这些影响的持续时间、适应性和耐受性仍有待阐明。
This study assessed the effects of acute intravenous L-tryptophan (neutral amino acid precursor for serotonin) administration on cocaine-induced dopaminergic responses. Male Sprague-Dawley rats were surgically implanted with guide cannulas in the nucleus accumbens 5 days prior to the study and with vascular catheters (carotid artery and jugular vein) on the day prior to the study. Using microdialysis, extracellular nucleus accumbens dopamine levels were measured in freely moving rats. Following a 2 h equilibration period, animals were randomized (n=7–8 per group) to receive either a constant intravenous (IV) infusion of L-tryptophan (200 mg/kg/h) or an equal volume (2 ml/h) of saline. Ninety minutes into the infusion, cocaine (20 mg/kg) was injected intra-peritoneally. Cocaine increased nucleus accumbens microdialysate dopamine levels (500% at 30 min). This was associated with marked hyperactivity. Tryptophan infusion elevated plasma tryptophan (8-fold), and blunted the cocaine-induced increase in nucleus accumbens microdialysate dopamine levels by ∼60%. Furthermore, tryptophan attenuated the cocaine-induced locomotor activity. These neurochemical and behavioral effects of tryptophan were associated with a marked increase in brain tissue serotonin content. The results of these studies demonstrate the feasibility of acute dietary manipulation of neurochemical and behavioral responses to cocaine. The duration, adaptation and tolerance to these effects remain to be elucidated.