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

• Published in: Behavioural brain research Vol. 244; pp. 58 - 65
• Main Authors: Kim, Taehyun, Hinton, David J., Johng, Sandy, Wang, Jia Bei, Choi, Doo-Sup
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.05.2013; Elsevier
• Subjects: AKT protein; Alcohol Drinking - blood; Alcohol Drinking - physiopathology; Alcohol Drinking - psychology; Animals; Behavioral psychophysiology; Berberine Alkaloids - pharmacology; Biological and medical sciences; Choice Behavior - drug effects; Choice Behavior - physiology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Dopamine Antagonists - pharmacology; Dopamine D2 receptor; Dopamine D2 Receptor Antagonists; Ethanol drinking; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; L-THP; Male; Mice; Oncogene Protein v-akt - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Signal Transduction - drug effects; Striatum; AC; DMSO; PKA; CPu; AKT; Ethanol drinking; NAc; Striatum; MEK; CREB; Dopamine D2 receptor; ANOVA; CeA; L-THP; ERK; Consumption; Ethanol; Rodentia; Central nervous system; Drinking; Basal ganglion; Corpus striatum; Encephalon; Signal transduction; Vertebrata; Mammalia; D2 Dopamine receptor; receptor; Mouse; Animal; Dopamine D
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2013.01.028

► An herb derived compound, levo-tetrahydropalmatine (L-THP) significantly attenuates ethanol drinking in mice. ► L-THP appears to inhibit dopamine D2 receptor in the dorsal striatum, not in the ventral striatum. ► Reduction of ethanol drinking by L-THP treatment is possibly correlated with D2R-mediated PKA signaling in the CPu. 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.