Rapid dopamine signaling in the nucleus accumbens during contingent and noncontingent cocaine administration

被引:164
作者
Stuber, GD
Roitman, MF
Phillips, PEM
Carelli, RM
Wightman, RM
机构
[1] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC USA
[3] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA
[4] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA
[5] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
[6] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA
关键词
dopamine; accumbens; cocaine; reinforcement; drug abuse; voltammetry;
D O I
10.1038/sj.npp.1300619
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cocaine acts as a reinforcer through its pharmacological effects on brain monoaminergic systems, which, through repeated pairings with environmental stimuli, lead to the development of conditioned effects of the drug. Both the pharmacological and conditioned aspects of cocaine are implicated in several facets of acquisition and maintenance of addiction, including drug craving. Here, we compare the effects of contingent (response dependent) and noncontingent (response independent) cocaine on rapid dopaminergic signaling in the core of the nucleus accumbens. Dopamine was monitored using fast-scan cyclic voltammetry. Noncontingent cocaine administered to both naive and animals with a history of self-administration resulted in a profound increase in the frequency of transient dopamine release events that are not time-locked to any specific environmental stimuli. Pharmacological effects were detectable approximately 40 s after cocaine administration. In contrast, when animals where allowed to self-administer cocaine on an FR-I schedule, dopamine transients (69 +/- 12 nM) were consistently observed time-locked to each reinforced response (peaking approximately 1.5 s after response completion). Importantly, no pharmacological effect of cocaine was observed within the Os following noncontingent cocaine administration, indicating that dopamine signals time-locked to the reinforced response are a result of the pairing of the operant behavior, the drug-associated cues, and cocaine. These data demonstrate that this pharmacological action of cocaine occurs for an extended period following either contingent or noncontingent administration, but is distinct from those dopamine transients that are time-locked to each lever-press in self-administering animals.
引用
收藏
页码:853 / 863
页数:11
相关论文
共 68 条
[61]   The addicted human brain: insights from imaging studies [J].
Volkow, ND ;
Fowler, JS ;
Wang, GJ .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (10) :1444-1451
[62]   Dopamine responses comply with basic assumptions of formal learning theory [J].
Waelti, P ;
Dickinson, A ;
Schultz, W .
NATURE, 2001, 412 (6842) :43-48
[63]   Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens [J].
Weiss, F ;
Maldonado-Vlaar, CS ;
Parsons, LH ;
Kerr, TM ;
Smith, DL ;
Ben-Shahar, O .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :4321-4326
[64]   Transient changes in mesolimbic dopamine and their association with 'reward' [J].
Wightman, RM ;
Robinson, DL .
JOURNAL OF NEUROCHEMISTRY, 2002, 82 (04) :721-735
[65]  
Wise R A., 1982, The Neural Basis of Feeding and reward, P445
[66]   Dopamine, learning and motivation [J].
Wise, RA .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (06) :483-494
[67]   FLUCTUATIONS IN NUCLEUS-ACCUMBENS DOPAMINE CONCENTRATION DURING INTRAVENOUS COCAINE SELF-ADMINISTRATION IN RATS [J].
WISE, RA ;
NEWTON, P ;
LEEB, K ;
BURNETTE, B ;
POCOCK, D ;
JUSTICE, JB .
PSYCHOPHARMACOLOGY, 1995, 120 (01) :10-20
[68]   Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission [J].
Wu, Q ;
Reith, MEA ;
Kuhar, MJ ;
Carroll, FI ;
Garris, PA .
JOURNAL OF NEUROSCIENCE, 2001, 21 (16) :6338-6347