Microinjection of M(5) Muscarinic Receptor Antisense Oligonucleotide into VTA Inhibits FosB Expression in the NAc and the Hippocampus of Heroin Sensitized Rats

Overview

Journal Neurosci Bull

Specialty Neurology

Date 2007 Jun 27

PMID 17592519

Citations 4

Authors

Hui-Fen Liu

Wen-Hua Zhou

Hua-Qiang Zhu

Miao-Jun Lai

Wei-Sheng Chen

Affiliations

Soon will be listed here.

Abstract

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.

Conclusion: 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.

Citing Articles

Transcriptional mechanisms of drug addiction .

Bali P, Kenny P Dialogues Clin Neurosci. 2020; 21(4):379-387.

PMID: 31949405 PMC: 6952748. DOI: 10.31887/DCNS.2019.21.4/pkenny.

Somatodendritic targeting of M5 muscarinic receptor in the rat ventral tegmental area: implications for mesolimbic dopamine transmission.

Garzon M, Pickel V J Comp Neurol. 2013; 521(13):2927-46.

PMID: 23504804 PMC: 4038040. DOI: 10.1002/cne.23323.

Review. Transcriptional mechanisms of addiction: role of DeltaFosB.

Nestler E Philos Trans R Soc Lond B Biol Sci. 2008; 363(1507):3245-55.

PMID: 18640924 PMC: 2607320. DOI: 10.1098/rstb.2008.0067.

Distinct patterns of DeltaFosB induction in brain by drugs of abuse.

Perrotti L, Weaver R, Robison B, Renthal W, Maze I, Yazdani S Synapse. 2008; 62(5):358-69.

PMID: 18293355 PMC: 2667282. DOI: 10.1002/syn.20500.

Recent progress in the research field of neuropharmacology in China.

Li J Cell Mol Neurobiol. 2008; 28(2):185-204.

PMID: 18240016 PMC: 11515025. DOI: 10.1007/s10571-007-9252-z.

References

Yamada M, Basile A, Fedorova I, Zhang W, Duttaroy A, Cui Y . Novel insights into M5 muscarinic acetylcholine receptor function by the use of gene targeting technology. Life Sci. 2003; 74(2-3):345-53. DOI: 10.1016/j.lfs.2003.09.022. View

Morgan J, Curran T . Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 1991; 14:421-51. DOI: 10.1146/annurev.ne.14.030191.002225. View

Nye H, Nestler E . Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. Mol Pharmacol. 1996; 49(4):636-45. View

Chen J, Kelz M, Hope B, Nakabeppu Y, Nestler E . Chronic Fos-related antigens: stable variants of deltaFosB induced in brain by chronic treatments. J Neurosci. 1997; 17(13):4933-41. PMC: 6573301. View

Forster G, Blaha C . Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci. 2003; 17(4):751-62. DOI: 10.1046/j.1460-9568.2003.02511.x. View

Bechara A, van der Kooy D . The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine. J Neurosci. 1989; 9(10):3400-9. PMC: 6569914. View

Liu H, Zhou W, Xie X, Cao J, Gu J, Yang G . [Muscarinic receptors modulate the mRNA expression of NMDA receptors in brainstem and the release of glutamate in periaqueductal grey during morphine withdrawal in rats]. Sheng Li Xue Bao. 2004; 56(1):95-100. View

Forster G, Blaha C . Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area. Eur J Neurosci. 2000; 12(10):3596-604. DOI: 10.1046/j.1460-9568.2000.00250.x. View

Kalivas P, Duffy P . Sensitization to repeated morphine injection in the rat: possible involvement of A10 dopamine neurons. J Pharmacol Exp Ther. 1987; 241(1):204-12. View

10.

Weiner D, Levey A, Brann M . Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. Proc Natl Acad Sci U S A. 1990; 87(18):7050-4. PMC: 54680. DOI: 10.1073/pnas.87.18.7050. View

11.

Robinson T, Berridge K . The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction. 2000; 95 Suppl 2:S91-117. DOI: 10.1080/09652140050111681. View

12.

Forster G, Yeomans J, Takeuchi J, Blaha C . M5 muscarinic receptors are required for prolonged accumbal dopamine release after electrical stimulation of the pons in mice. J Neurosci. 2002; 22(1):RC190. PMC: 6757584. View

13.

Pierce R, Kalivas P . A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev. 1997; 25(2):192-216. DOI: 10.1016/s0165-0173(97)00021-0. View

14.

Labiner D, Butler L, Cao Z, Hosford D, Shin C, McNamara J . Induction of c-fos mRNA by kindled seizures: complex relationship with neuronal burst firing. J Neurosci. 1993; 13(2):744-51. PMC: 6576657. View

15.

Kelz M, Chen J, Carlezon Jr W, Whisler K, GILDEN L, Beckmann A . Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature. 1999; 401(6750):272-6. DOI: 10.1038/45790. View

16.

Thomsen M, Woldbye D, Wortwein G, Fink-Jensen A, Wess J, Caine S . Reduced cocaine self-administration in muscarinic M5 acetylcholine receptor-deficient mice. J Neurosci. 2005; 25(36):8141-9. PMC: 6725551. DOI: 10.1523/JNEUROSCI.2077-05.2005. View

17.

Chaudhuri A . Neural activity mapping with inducible transcription factors. Neuroreport. 1997; 8(13):iii-vii. View

18.

Vilaro M, Palacios J, Mengod G . Localization of m5 muscarinic receptor mRNA in rat brain examined by in situ hybridization histochemistry. Neurosci Lett. 1990; 114(2):154-9. DOI: 10.1016/0304-3940(90)90064-g. View

19.

Fink-Jensen A, Fedorova I, Wortwein G, Woldbye D, Rasmussen T, Thomsen M . Role for M5 muscarinic acetylcholine receptors in cocaine addiction. J Neurosci Res. 2003; 74(1):91-6. DOI: 10.1002/jnr.10728. View

20.

Basile A, Fedorova I, Zapata A, Liu X, Shippenberg T, Duttaroy A . Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia. Proc Natl Acad Sci U S A. 2002; 99(17):11452-7. PMC: 123277. DOI: 10.1073/pnas.162371899. View