Faculty Collaboration Database

Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. Pharmacol Biochem Behav 2010 Dec;97(2):310-6

Date

09/08/2010

Pubmed ID

20816889

Pubmed Central ID

PMC2956862

DOI

10.1016/j.pbb.2010.08.016

Scopus ID

2-s2.0-77957811262 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese herbal preparations and has a unique pharmacological profile that includes dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced reinstatement in rats at doses that do not alter food-reinforced responding. This study examined the effects of l-THP on cocaine and food SA under progressive-ratio (PR) schedules of reinforcement and the discriminative stimulus effects of cocaine. In adult male Sprague-Dawley rats self-administering cocaine (0.5 or 1.0mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5mg/kg doses. l-THP also reduced the breaking point and response rate for PR SA of sucrose-sweetened food pellets, although the decrease was significant only at the 7.5mg/kg l-THP dose. In rats trained to discriminate cocaine (10mg/kg, ip) from saline, l-THP (1.875, 3.75 and 7.5mg/kg) produced a rightward shift in the dose-response curve for cocaine generalization. During generalization testing, l-THP reduced response rate, but only at the 7.5mg/kg dose. l-THP also prevented substitution of the dopamine D2/D3 receptor agonist, (±) 7-OH-DPAT, for cocaine suggesting a potential role for antagonism of D2 and/or D3 receptors in the effects of l-THP. These data further demonstrate that l-THP attenuates the reinforcing and subjective effects of cocaine at doses that do not produce marked motor effects and provide additional evidence that l-THP may have utility for the management of cocaine addiction.

Author List

Mantsch JR, Wisniewski S, Vranjkovic O, Peters C, Becker A, Valentine A, Li SJ, Baker DA, Yang Z

Author

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

Adrenergic Agents
Animals
Berberine Alkaloids
Cocaine
Cocaine-Related Disorders
Conditioning, Operant
Dopamine Agonists
Dopamine Uptake Inhibitors
Dose-Response Relationship, Drug
Male
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D2
Receptors, Dopamine D3
Reinforcement Schedule
Self Administration
Tetrahydronaphthalenes