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Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats. Drug Alcohol Depend 2011 Jul 01;116(1-3):72-9



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-79957593608   37 Citations


Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0mg/kg l-THP 1h prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0mg/kg, l-THP dose, indicating that the effects of 3mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction.

Author List

Figueroa-Guzman Y, Mueller C, Vranjkovic O, Wisniewski S, Yang Z, Li SJ, Bohr C, Graf EN, Baker DA, Mantsch JR


Shi-Jiang Li PhD Professor in the Biophysics department at Medical College of Wisconsin
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Behavior, Addictive
Berberine Alkaloids
Cocaine-Related Disorders
Dopamine Antagonists
Dopamine Uptake Inhibitors
Dose-Response Relationship, Drug
Plant Preparations
Plant Roots
Rats, Sprague-Dawley
Secondary Prevention
Self Administration
Stress, Physiological