Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats.

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Research Abstract Details 

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Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Abstract Text:

Zheng-Xiong Xi,Zheng Yang,Shi-Jiang Li,Xia Li,Christopher Dillon,Xiao-Qing Peng,Krista Spiller,Eliot L Gardner,Zheng-Xiong Xi,Zheng Yang,Shi-Jiang Li,Xia Li,Christopher Dillon,Xiao-Qing Peng,Krista Spiller,Eliot L Gardner,

It was recently reported that levo-tetrahydropalmatine (l-THP), a dopamine (DA) D1 and D2 receptor antagonist purified from the Chinese herb Stephanie, appears to be effective in attenuating cocaine self-administration, cocaine-triggered reinstatement and cocaine-induced conditioned place preference in preclinical animal models. The present study was designed to contrast l-THP's effects on cocaine self-administration under fixed-ratio (FR) and progressive-ratio (PR) reinforcement, and to study l-THP's effects on cocaine-enhanced brain stimulation reward (BSR). Systemic administration of l-THP produced dose-dependent, biphasic effects, i.e., low-to-moderate doses (1, 3, 10 mg/kg) increased, while a high dose (20 mg/kg) inhibited cocaine self-administration behavior under FR2 reinforcement. The increased cocaine self-administration is likely a compensatory response to a reduction in cocaine's rewarding effects, because the same low doses of l-THP dose-dependently attenuated cocaine self-administration under PR reinforcement and also attenuated cocaine-enhanced BSR. These attenuations of PR cocaine self-administration and cocaine-enhanced BSR are unlikely due to l-THP-induced sedation or locomotor inhibition, because only 10 mg/kg, but not 1-3 mg/kg, of l-THP inhibited locomotion, sucrose self-administration and asymptotic operant performance in the BSR paradigm. In vivo microdialysis demonstrated that l-THP slightly elevates extracellular nucleus accumbens DA by itself, but dose-dependently potentiates cocaine-augmented DA, suggesting that a postsynaptic, rather than presynaptic, DA receptor antagonism underlies l-THP's actions on cocaine reward. Together, the present data, combined with previous findings, support the potential use of l-THP for treatment of cocaine addiction.

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Publishing Authors By Initials

ZX Xi,Z Yang,SJ Li,X Li,C Dillon,XQ Peng,K Spiller,EL Gardner,ZX Xi,Z Yang,SJ Li,X Li,C Dillon,XQ Peng,K Spiller,EL Gardner,

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Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuropharmacology

VOLUME: 53

Page Numbers: 771-82

Journal Abbreviation: Neuropharmacology

ISSN: 0028-3908

DAY: 15

MONTH: 08

YEAR: 2007

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Information

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LANGUAGE: eng

NlmUniqueID: 236217

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Grant and Affiliation Information for Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats.

AFFILIATION: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. zxi@intra.nida.nih.gov

Country: England

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MEDLINETA: Neuropharmacology

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