Levo-tetrahydropalmatine decreases ethanol drinking and antagonizes dopamine D2 receptor-mediated signaling in the mouse dorsal striatum

Taehyun Kim, David J. Hinton, Sandy Johng, Jia Bei Wang, Doo Sup Choi

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

An herb derived compound, levo-tetrahydropalmatine (L-THP), attenuates self-administration of cocaine and opiates in rodents. Since L-THP mainly antagonizes dopamine D2 receptors (D2R) in the brain, it is likely to regulate other addictive behaviors as well. Here, we examined whether L-THP regulates ethanol drinking in C57BL/6J mice using a two-bottle choice drinking experiment. L-THP treated mice consumed less ethanol compared to vehicle-treated mice during the 15% ethanol drinking session while water consumption remained similar between each group. We then examined the molecular basis underlying the pharmacological effect of L-THP in mice. Our results indicated that a single injection of L-THP increased active phosphorylated forms of PKA, AKT and ERK in the caudate-putamen (CPu), but not in the nucleus accumbens (NAc), of alcohol naïve mice. Interestingly, we found that systematic treatment with L-THP for 4 consecutive days while mice were drinking 15% ethanol increased pPKA levels in the CPu, but not in the NAc. In contrast to the effect of acute L-THP treatment, no differences were detected for pAKT or pERK in either striatal regions. Together, our findings suggest that reduction of ethanol drinking by L-THP treatment is possibly correlated with D2R-mediated PKA signaling in the CPu.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalBehavioural Brain Research
Volume244
DOIs
StatePublished - May 1 2013

Keywords

  • Dopamine D receptor
  • Ethanol drinking
  • L-THP
  • Striatum

ASJC Scopus subject areas

  • Behavioral Neuroscience

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