Chronic Cocaine Administration Increases CNS Tyrosine Hydroxylase Enzyme Activity and mRNA Levels and Tryptophan Hydroxylase Enzyme Activity Levels
Chronic Cocaine Administration Increases CNS Tyrosine Hydroxylase Enzyme Activity and mRNA Levels and Tryptophan Hydroxylase Enzyme Activity Levels
复制标题
长期服用可卡因会增加中枢神经系统酪氨酸羟化酶活性和 mRNA 水平以及色氨酸羟化酶活性水平
作者：
S. Vrana;K. Vrana;T. Koves;James E. Smith;S. Dworkin
可卡因是突触终末再摄取多巴胺和5-羟色胺的抑制剂，具有强大的强化作用，导致滥用可卡因。酪氨酸羟基酶(TH)和色氨酸羟基酶(TPH)分别催化多巴胺和5-羟色胺生物合成的限速步骤，是对可卡因作用敏感的动态调节机制的主题。这项研究评估了慢性可卡因对大脑TH和TPH活性的影响。注射可卡因(0.33 mg/次，静脉注射)给大鼠连续7天，每8分钟一次，每天6小时。这种给药时间表类似于大鼠在随意获得该剂量时的自我给药模式。这种慢性非反应性给药增加了黑质(30%)和腹侧被盖区(43%)的TH酶活性。此外，TH基因的表达水平也增加了(分别为45%和50%)。与细胞体的酶和分子生物学变化相反，终末区域(纹状体和伏隔核)的TH活性没有变化。同样，TPH活性在中缝核(5-羟色胺能细胞体)增加了50%。综上所述，慢性非反应依赖的可卡因给药增加了运动(黑质纹状体)和强化(中边缘)多巴胺通路胞体中TH基因的表达和活性。这些增加并没有表现在这些通路的终端场中。
Cocaine is an inhibitor of dopamine and serotonin reuptake by synaptic terminals and has potent reinforcing effects that lead to its abuse. Tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) catalyze the rate‐limiting steps in dopamine and serotonin biosynthesis, respectively, and are the subject of dynamic regulatory mechanisms that could be sensitive to the actions of cocaine. This study assessed the effects of chronic cocaine on brain TH and TPH activities. Cocaine was administered (0.33 mg/infusion, i.v.) to rats for 7 days every 8 min for 6 h per day. This administration schedule is similar to patterns of self‐administration by rats when given ad libitum access to this dose. This chronic, response‐independent administration increased TH enzyme activity in the substantia nigra (30%) and ventral tegmental area (43%). Moreover, TH mRNA levels were also increased (45 and 50%, respectively). In contrast to the enzymatic and molecular biological changes in the cell bodies, TH activity was unchanged in the terminal fields (corpus striaturn and nucleus accumbens). Similarly, TPH activity was increased by 50% in the raphe nucleus (serotonergic cell bodies). In summary, the chronic response‐independent administration of cocaine produces increases in the expression of TH mRNA and activity in both the cell bodies of motor (nigrostriatal) and reinforcement (mesolimbic) dopamine pathways. These increases are not manifested in the terminal fields of these pathways.
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影响因子：
13.9
作者：
R. Zigmond;M. Schwarzschild;A. Rittenhouse
通讯作者：
R. Zigmond;M. Schwarzschild;A. Rittenhouse
DOI：
10.1073/pnas.87.17.6912
发表时间：
1990-09-01
影响因子：
11.1
作者：
GRAYBIEL, AM;MORATALLA, R;ROBERTSON, HA
通讯作者：
ROBERTSON, HA
可卡因的神经行为药理学。
DOI：
--
发表时间：
1988
期刊：
NIDA research monograph
影响因子：
--
作者：
Dworkin,SI;Smith,JE
通讯作者：
Smith,JE
行为控制在分析正在进行的事件中的重要性。
DOI：
--
发表时间：
1992
期刊：
NIDA research monograph
影响因子：
--
作者：
Dworkin,SI;Porrino,LJ;Smith,JE
通讯作者：
Smith,JE
DOI：
10.1073/pnas.84.16.5530
发表时间：
1987-08-01
影响因子：
11.1
作者：
GRENETT, HE;LEDLEY, FD;WOO, SLC
通讯作者：
WOO, SLC