TY - JOUR
T1 - Levo-tetrahydropalmatine decreases ethanol drinking and antagonizes dopamine D2 receptor-mediated signaling in the mouse dorsal striatum
AU - Kim, Taehyun
AU - Hinton, David J.
AU - Johng, Sandy
AU - Wang, Jia Bei
AU - Choi, Doo Sup
N1 - Funding Information:
We thank Sun Choi and Denise Walker for expert technical assistance, Christina Ruby for advice for behavioral experiments, as well as Hyung Nam and Steve Brimijoin for helpful discussion. This project was funded by the Samuel Johnson Foundation for Genomics of Addiction Program at Mayo Clinic and by grants from the National Institutes of Health (NIH) to D. -S. C . ( P20 AA017830-Project 1 ).
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - Dopamine D receptor
KW - Ethanol drinking
KW - L-THP
KW - Striatum
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U2 - 10.1016/j.bbr.2013.01.028
DO - 10.1016/j.bbr.2013.01.028
M3 - Article
C2 - 23376703
AN - SCOPUS:84874390309
SN - 0166-4328
VL - 244
SP - 58
EP - 65
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -