Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats

John R. Mantsch*, Samantha Wisniewski, Oliver Vranjkovic, Corey Peters, Amanda Becker, Abbey Valentine, Shi Jiang Li, David A. Baker, Zheng Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus 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 1.0. 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.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume97
Issue number2
DOIs
StatePublished - Dec 2010

Keywords

  • 7-OH-DPAT
  • Antagonist
  • D2 receptor
  • D3 receptor
  • Discriminative stimulus
  • Dopamine
  • THP

ASJC Scopus subject areas

  • Biological Psychiatry
  • Biochemistry
  • Behavioral Neuroscience
  • Clinical Biochemistry
  • Toxicology
  • Pharmacology

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