Levo-Tetrahydropalmatine Attenuates Cocaine Self-Administration under a Progressive-Ratio Schedule and Cocaine Discrimination in Rats

Authors

John R. Mantsch, Marquette UniversityFollow
Samantha Wisniewski, Marquette University
Oliver Vranjkovic, Marquette University
Corey Peters, Marquette University
Amanda Becker, Marquette University
Abbey Valentine, Marquette University
Shi-Jiang Li, Medical College of Wisconsin
David A. Baker, Marquette UniversityFollow
Zheng Yang, Beijing Institute of Basic Medical Sciences

Document Type

Article

Language

eng

Publication Date

12-2010

Publisher

Elsevier

Source Publication

Pharmacology Biochemistry and Behavior

Source ISSN

0091-3057

Original Item ID

DOI: 10.1016/j.pbb.2010.08.016

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 1.0 mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5 mg/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 7.5 mg/kg l-THP dose. In rats trained to discriminate cocaine (10 mg/kg, ip) from saline, l-THP (1.875, 3.75 and 7.5 mg/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 7.5 mg/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.

Comments

Accepted version. Pharmacology Biochemistry and Behavior, Vol. 97, No. 2 (2010). DOI. © 2010 Elsevier. Used with permission.

Recommended Citation

Mantsch, John R.; Wisniewski, Samantha; Vranjkovic, Oliver; Peters, Corey; Becker, Amanda; Valentine, Abbey; Li, Shi-Jiang; Baker, David A.; and Yang, Zheng, "Levo-Tetrahydropalmatine Attenuates Cocaine Self-Administration under a Progressive-Ratio Schedule and Cocaine Discrimination in Rats" (2010). Biomedical Sciences Faculty Research and Publications. 10.
https://epublications.marquette.edu/biomedsci_fac/10