title: Levo-tetrahydropalmatine decreases ethanol drinking and antagonizes dopamine D2 receptor-mediated signaling in the mouse dorsal striatum.
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.
authors: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Taehyun
authors: T
authors: Kim
authors: David J
authors: DJ
authors: Hinton
authors: Sandy
authors: S
authors: Johng
authors: Jia Bei
authors: JB
authors: Wang
authors: Doo-Sup
authors: DS
authors: Choi
mesh_terms: D000428:Alcohol Drinking / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001600:Berberine Alkaloids; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C014215:tetrahydropalmatine; D051058:Oncogene Protein v-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
references: Psychopharmacology (Berl). 2008 Aug;199(3):403-19
references: 18283437
references: J Neurochem. 2001 Apr;77(1):326-35
references: 11279288
references: Life Sci. 1984 Dec 3;35(23):2281-96
references: 6390056
references: Neurosci Lett. 2005 Aug 5;383(3):328-32
references: 15871910
references: Neuron. 2011 Jun 9;70(5):979-90
references: 21658589
references: Yao Xue Xue Bao. 1996;31(9):652-6
references: 9863229
references: Biol Psychiatry. 2011 Jun 1;69(11):1043-51
references: 21489406
references: Eur J Pharmacol. 2009 Jan 14;602(2-3):321-7
references: 19071107
references: Drug Alcohol Depend. 2011 Jul 1;116(1-3):72-9
references: 21196089
references: Psychopharmacology (Berl). 2009 May;204(1):135-47
references: 19125235
references: Eur J Neurosci. 2008 Oct;28(8):1437-48
references: 18793321
references: Biol Psychiatry. 2011 Sep 15;70(6):575-82
references: 21549353
references: Pharmacol Biochem Behav. 2010 Dec;97(2):310-6
references: 20816889
references: Alcohol. 2008 Mar;42(2):91-7
references: 18358987
references: J Neurosci. 2006 Aug 9;26(32):8320-31
references: 16899727
references: Front Mol Neurosci. 2011 Nov 01;4:38
references: 22065948
references: Zhongguo Yao Li Xue Bao. 1999 Aug;20(8):715-9
references: 10678104
references: Anesth Analg. 2007 Jul;105(1):89-96
references: 17578962
references: J Neurosci. 2000 May 15;20(10):RC75
references: 10783399
references: Cell Mol Neurobiol. 2008 Jun;28(4):491-9
references: 17710533
references: Acta Pharmacol Sin. 2008 Jul;29(7):781-8
references: 18565275
references: Alcohol Clin Exp Res. 2011 Jan;35(1):99-107
references: 21039631
references: Eur J Pharmacol. 1987 Apr 14;136(2):263-4
references: 2954833
references: Sci Sin B. 1986 May;29(5):527-34
references: 2880397
references: Neuroscience. 2000;96(3):451-74
references: 10717427
references: Neuropsychopharmacology. 1998 Feb;18(2):63-101
references: 9430133
references: Eur J Pharmacol. 1986 Jan 21;120(2):217-26
references: 3948920
references: Alcohol Clin Exp Res. 2003 Mar;27(3):396-409
references: 12658105
references: Physiol Rev. 2009 Apr;89(2):649-705
references: 19342616