Dissociable Rate-Dependent Effects of Oral Methylphenidate on Impulsivity and D2/3 Receptor Availability in the Striatum

被引：48

作者：

Caprioli, Daniele ^{[1
]}

Jupp, Bianca ^{[2
,3
]}

Hong, Young T. ^{[4
]}

Sawiak, Stephen J. ^{[2
,4
]}

Ferrari, Valentina ^{[4
]}

Wharton, Laura ^{[2
,3
]}

Williamson, David J. ^{[4
]}

McNabb, Carolyn ^{[5
]}

Berry, David ^{[6
]}

Aigbirhio, Franklin I. ^{[2
,4
]}

Robbins, Trevor W. ^{[2
,3
]}

Fryer, Tim D. ^{[2
,4
]}

Dalley, Jeffrey W. ^{[2
,3
,7
]}

机构：

[1] NIDA, Dept Hlth & Human Serv, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA

[2] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England

[3] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England

[4] Univ Cambridge, Wolfson Brain Imaging Ctr, Dept Clin Neurosci, Cambridge CB2 0QQ, England

[5] Univ Auckland, Sch Pharm, Auckland 1142, New Zealand

[6] Epilepsy Soc, Gerrards Cross SL9 0RJ, England

[7] Univ Cambridge, Dept Psychiat, Cambridge CB2 2QQ, England

来源：

JOURNAL OF NEUROSCIENCE | 2015年 / 35卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

addiction; attention-deficit hyperactivity disorder; dopamine; methylphenidate; nucleus accumbens; positron emission tomography; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; REACTION-TIME-TASK; DEFICIT HYPERACTIVITY DISORDER; PSYCHOMOTOR STIMULANT-DRUGS; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; BEHAVIORAL PHARMACOLOGY; VENTRAL STRIATUM; ADOLESCENT RATS; WORKING-MEMORY;

D O I：

10.1523/JNEUROSCI.3890-14.2015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We have previously shown that impulsivity in rats is linked to decreased dopamineD(2/3) receptor availability in the ventral striatum. In the present study, we investigated, using longitudinal positron emission tomography (PET), the effects of orally administered methylphenidate (MPH), a first-line treatment for attention deficit hyperactivity disorder, on D-2/3 receptor availability in the dorsal and ventral striatum and related these changes to impulsivity. Rats were screened for impulsive behavior on a five-choice serial reaction time task. After a baseline PET scan with the D-2/3 ligand [F-18] fallypride, rats received 6 mg/kg MPH, orally, twice each day for 28 d. Rats were then reassessed for impulsivity and underwent a second [F-18] fallypride PET scan. Before MPH treatment, we found that D-2/3 receptor availability was significantly decreased in the left but not the right ventral striatum of high-impulse (HI) rats compared with low-impulse (LI) rats. MPH treatment increased impulsivity in LI rats, and modulated impulsivity and D-2/3 receptor availability in the dorsal and ventral striatum of HI rats through inverse relationships with baseline levels of impulsivity and D-2/3 receptor availability, respectively. However, we found no relationship between the effects of MPH on impulsivity and D-2/3 receptor availability in any of the striatal subregions investigated. These findings indicate that trait-like impulsivity is associated with decreased D-2/3 receptor availability in the left ventral striatum, and that stimulant drugs modulate impulsivity and striatal D-2/3 receptor availability through independent mechanisms.

引用

页码：3747 / 3755

页数：9

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