Speedball induced changes in electrically stimulated dopamine overflow in rat nucleus accumbens

NEUROPHARMACOLOGY

卷:60

Article

Pattison, Lindsey P.¹  Bonin, Keith D.²  Hemby, Scott E.^1,3  Budygin, Evgeny A.¹ 

[1] Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27101 USA

[2] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA

[3] Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27101 USA

关键词: Cocaine;    Heroin;    Speedball;    Dopamine;    Uptake;    Release;    Voltammetry;   

DOI  :  10.1016/j.neuropharm.2010.09.014

来源: Elsevier

【 摘 要 】

Cocaine/heroin combinations (speedball) induce a synergistic elevation in extracellular dopamine concentrations ([DA](e)) in the nucleus accumbens (NAc) that can explain the increased abuse liability of speedball. To further delineate the mechanism of this neurochemical synergism, in vivo fast-scan cyclic voltammetry (FSCV) was used to compare NAc DA release and reuptake kinetic parameters following acute administration of cocaine, heroin and speedball in drug-naive rats. These parameters were extracted from accumbal DA overflow induced by electrical stimulation of the ventral tegmental area. Evoked DA efflux was increased following both cocaine and speedball delivery, whereas heroin did not significantly change evoked DA release from baseline. DA efflux was significantly greater following cocaine compared to speedball. However, DA transporter (DAT) apparent affinity (K-m) values were similarly elevated following cocaine and speedball administration, but unaffected by heroin. Neither drug induced substantial changes in the maximal reuptake rate (V-max). These data, combined with published microdialysis and electrophysiological results, indicate that the combination of cocaine-induced competitive inhibition of DAT and the increase in the DA release elicited by heroin is responsible for the synergistic increase in ([DA](e)) induced by speedball. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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