Serotonin (5-hydroxytryptamine) 5-HT2A receptor: association with inherent and cocaine-evoked behavioral disinhibition in rats

被引:43
作者
Anastasio, Noelle C. [1 ,2 ]
Stoffel, Erin C. [1 ,2 ]
Fox, Robert G. [1 ,2 ]
Bubar, Marcy J. [1 ,2 ]
Rice, Kenner C. [4 ]
Moeller, Frederick G. [1 ,3 ]
Cunningham, Kathryn A. [1 ,2 ]
机构
[1] Univ Texas Galveston, Med Branch, Ctr Addict Res, Galveston, TX 77555 USA
[2] Univ Texas Galveston, Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA
[3] Univ Texas Houston, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX 77225 USA
[4] NIDA, Chem Biol Res Branch, Drug Design & Synth Sect, Intramural Res Program,NIH, Bethesda, MD 20892 USA
来源
BEHAVIOURAL PHARMACOLOGY | 2011年 / 22卷 / 03期
关键词
behavioral disinhibition; cocaine; differential reinforcement of low rate task; 5-HT2A receptor; impulsivity; one-choice serial reaction time task; rat; REACTION-TIME-TASK; DISCRIMINATIVE STIMULUS PROPERTIES; SCHEDULE-CONTROLLED BEHAVIOR; INDUCED LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; IMPULSIVE CHOICE; SEEKING BEHAVIOR; DOPAMINERGIC MECHANISMS; EXTRACELLULAR DOPAMINE;
D O I
10.1097/FBP.0b013e328345f90d
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT2AR as an important regulatory substrate in impulse control. Behavioural Pharmacology 22: 248-261 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:248 / 261
页数:14
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