TY - JOUR
T1 - Low doses of dextromethorphan attenuate morphine-induced rewarding via the sigma-1 receptor at ventral tegmental area in rats
AU - Chen, Shiou Lan
AU - Hsu, Kuei Ying
AU - Huang, Eagle Yi Kung
AU - Lu, Ru Band
AU - Tao, Pao Luh
N1 - Funding Information:
This study was supported in part by grants from the National Health Research Institutes (NHRI-EX97-9401NP, NHRI-99A1-PDCO-0809111), Taiwan, Republic of China and National Cheng Kung University Project of Promoting Academic Excellence & Developing World Class Research Centers, Taiwan, Republic of China.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20. mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5. mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3. mg/kg, i.p.). When BD1047 (5. nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics.
AB - Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20. mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5. mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3. mg/kg, i.p.). When BD1047 (5. nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics.
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U2 - 10.1016/j.drugalcdep.2011.01.013
DO - 10.1016/j.drugalcdep.2011.01.013
M3 - Article
C2 - 21320758
AN - SCOPUS:79960840358
SN - 0376-8716
VL - 117
SP - 164
EP - 169
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 2-3
ER -