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. 2007 Dec 15;23(1):1–8. doi: 10.1007/s12264-007-0001-6

Microinjection of M5 muscarinic receptor antisense oligonucleotide into VTA inhibits FosB expression in the NAc and the hippocampus of heroin sensitized rats

中脑腹侧被盖区注射M5 受体反义寡核苷酸抑制海洛因敏化大鼠伏隔核和海马中FosB 表达

Hui-Fen Liu 1,✉, Wen-Hua Zhou 1, Hua-Qiang Zhu 1, Miao-Jun Lai 1, Wei-Sheng Chen 1
PMCID: PMC5500770  PMID: 17592519

Abstract

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 hippocampus 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.

Keywords: Heroin, locomotor activity, muscarinic receptor, FosB, nucleus accumbens, hippocampus

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