Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocam...Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides （AS-ONs） targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area （VTA） blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus （DG） of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide （S-ONs） into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.展开更多
This study was carried out in the Wistar rats to investigate the effect of Tang herb on the pharmacokinetics of the antiretroviral drug lopinavir （LPV） following single oral administration. Rats were randomly divide...This study was carried out in the Wistar rats to investigate the effect of Tang herb on the pharmacokinetics of the antiretroviral drug lopinavir （LPV） following single oral administration. Rats were randomly divided into LPV group （36 mg/kg） and LPV combining with Tang herb group （LPV： 36 mg/kg, Tang herb： 864 mg/kg）. The blood concentrations of lopinavir at 0, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 22 h after administration were determined by HPLC and the pharmacokinetic parameters were investigated. The results showed that Tang herb significantly increased the Cmax and A UC （P〈0.05） while slightly increased the t1/2z and Tmax of lopinavir （P〉0.05）. The present study suggests that Tang herb may delay the absorption, increase the time to reach the maximum concentration, and improve the bioavailability of LPV. Further evaluation of the possible interaction mechanism between Tang herb and LPV needs to be studied.展开更多
基金This work was supported by the National Nature Science Foundation of China （No.30470554）the National Basic Research Development Program of China（No.2003CB515404）.
文摘Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides （AS-ONs） targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area （VTA） blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus （DG） of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide （S-ONs） into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.
基金Major New Drug Discovery Science and Technology Group(Grant No.2012ZX09303013)
文摘This study was carried out in the Wistar rats to investigate the effect of Tang herb on the pharmacokinetics of the antiretroviral drug lopinavir （LPV） following single oral administration. Rats were randomly divided into LPV group （36 mg/kg） and LPV combining with Tang herb group （LPV： 36 mg/kg, Tang herb： 864 mg/kg）. The blood concentrations of lopinavir at 0, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 22 h after administration were determined by HPLC and the pharmacokinetic parameters were investigated. The results showed that Tang herb significantly increased the Cmax and A UC （P〈0.05） while slightly increased the t1/2z and Tmax of lopinavir （P〉0.05）. The present study suggests that Tang herb may delay the absorption, increase the time to reach the maximum concentration, and improve the bioavailability of LPV. Further evaluation of the possible interaction mechanism between Tang herb and LPV needs to be studied.
