In vivo comparison of harmine efficacy against psychostimulants: Preferential inhibit\ion of the cocaine response through a glutamatergic mechanism

NEUROSCIENCE LETTERS

卷:525

Article

Owaisat, Suzan³  Raffa, Robert B.³  Rawls, Scott M.^1,2 

[1] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA

[2] Temple Univ, Ctr Substance Abuse Res, Philadelphia, PA 19122 USA

[3] Temple Univ, Sch Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19122 USA

关键词: Harmine;    beta-Carboline;    Mephedrone;    Cocaine;    Glutamate;    Planaria;   

DOI  :  10.1016/j.neulet.2012.07.052

来源: Elsevier

【 摘 要 】

Harmine is a beta-carboline compound that targets glutamatergic, monoaminergic, and GABAergic pathways underlying drug addiction. We compared the efficacy of harmine against different psychoactive drugs using an invertebrate (planarian) assay designed to quantify 'C-shape' responses. Harmine itself (0.01-10 mu M) did not produce C-shapes. However, when applied over the same concentration range, harmine significantly inhibited C-shapes elicited by cocaine, with a concentration of 0.1 mu M producing almost 90% inhibition. Consistent with its putative actions, harmine produced a similar, though less efficacious, inhibition of C-shapes elicited by the substituted amphetamines methamphetamine and mephedrone (4-methylmethcathinone) but was much less effective against nicotine. When tested in the presence of the glutamate transporter inhibitor dihydrokainate (DHK) (0.1, 1 mu M), harmine (0.1 mu M) efficacy against cocaine-induced C-shapes was significantly reduced. Harmine also attenuated C-shapes elicited by N-methyl-D-aspartate (NMDA) and by glutamate itself. The present data suggest that harmine displays preferential efficacy against different addictive substances (cocaine > amphetamines > nicotine) and, at least for cocaine, is dependent on the glutamate system. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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