Microinjection of M(5) muscarinic receptor antisense oligonucleotide into VTA inhibits FosB expression in the NAc and the hippocampus of heroin sensitized rats.
OBJECTIVE
To investigate the effect of M(5) 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 M(5) muscarinic receptor was transferred with the lipofectin.


RESULTS
Microinjection of AS-ONs targeting M(5) 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 M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) 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.


CONCLUSIONS
Blocking M(5) 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. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.
Liu
Hui-Fen
HF
Ningbo Institute of Microcirculation and Henbane, Ningbo Addiction Research and Treatment Center, Ningbo 315010, China. lihufen@163.com
Zhou
Wen-Hua
WH
Zhu
Hua-Qiang
HQ
Lai
Miao-Jun
MJ
Chen
Wei-Sheng
WS
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D003932:Heroin / Q000009:adverse effects; D006556:Heroin Dependence / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000009:adverse effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043642:Receptor, Muscarinic M5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
C483820:Fosb protein, rat; D009294:Narcotics; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D043642:Receptor, Muscarinic M5; D003932:Heroin; D000109:Acetylcholine