KEGG   PATHWAY: mna05033
Entry
mna05033                    Pathway                                

Name
Nicotine addiction - Miniopterus natalensis
Description
Nicotine is one of the main psychoactive ingredients in tobacco that contributes to the harmful tobacco smoking habit. A common feature of addictive drugs, including nicotine, is that they increase dopamine (DA) release in the nucleus accumbens (NAc). The principal dopaminergic projections to NAc arise from neurons in the ventral tegmental area (VTA). In the VTA, alpha6- and alpha4beta2-containing nAChRs (alpha6*-AChRs and alpha4beta2*-AChRs, respectively) are located on GABAergic terminals and provide inhibitory inputs onto DAergic neuons, while alpha7*-nAChRs are located on glutamatergic terminals and activation of these receptors enhances glutamate release and increases excitability of DAergic neurons. Nicotine acts as an agonist to activate and desensitize these nicotinic acetylcholine receptors (nAChRs). After a short exposure to nicotine, alpha6*- and alpha4beta2*- nAChRs on GABAergic afferents are desensitized, decreasing GABA release and decreasing local inhibition of DA neurons. But the alpha7*-nAChRs on glutamatergic afferents remain active and enhance glutamate excitation of the DA neurons, leading to increased DA release in the NAc -and so facilitate the reinforcing effects of nicotine.
Class
Human Diseases; Substance dependence
Pathway map
mna05033  Nicotine addiction
mna05033

Other DBs
GO: 0035094
Organism
Miniopterus natalensis [GN:mna]
Gene
107542119  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
107523942  CHRNA6; neuronal acetylcholine receptor subunit alpha-6 [KO:K04808]
107541038  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
107536136  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
107529071  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 isoform X1 [KO:K04806]
107543725  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
107537889  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
107537965  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X1 [KO:K05175]
107537858  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
107527865  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
107532500  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175]
107533097  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
107528034  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
107537880  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
107533104  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
107537863  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
107527855  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
107532484  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 isoform X1 [KO:K05186]
107540159  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
107537955  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit epsilon-like [KO:K05185]
107537964  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
107540343  GABRP; gamma-aminobutyric acid receptor subunit pi [KO:K05189]
107533430  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190]
107533431  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
107527103  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
107528546  SLC17A6; vesicular glutamate transporter 2 [KO:K12302]
107545115  SLC17A8; vesicular glutamate transporter 3 isoform X1 [KO:K12302]
107531888  SLC17A7; vesicular glutamate transporter 1 [KO:K12302]
107527910  neuronal acetylcholine receptor subunit alpha-7 [KO:K04809]
107536149  GRIN1; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 1 [KO:K05208]
107525462  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
107525331  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
107542924  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
107531815  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
107546596  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
107534564  GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214]
107537716  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
107527540  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
107524995  GRIA3; glutamate receptor 3 [KO:K05199]
107532917  GRIA4; glutamate receptor 4 isoform X1 [KO:K05200]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00334  4-Aminobutanoate
C00698  Cl-
C00745  Nicotine
C01330  Sodium cation
C01996  Acetylcholine
Reference
  Authors
Mansvelder HD, McGehee DS
  Title
Cellular and synaptic mechanisms of nicotine addiction.
  Journal
J Neurobiol 53:606-17 (2002)
DOI:10.1002/neu.10148
Reference
  Authors
Wonnacott S, Sidhpura N, Balfour DJ
  Title
Nicotine: from molecular mechanisms to behaviour.
  Journal
Curr Opin Pharmacol 5:53-9 (2005)
DOI:10.1016/j.coph.2004.12.002
Reference
  Authors
Mao D, McGehee DS
  Title
Nicotine and behavioral sensitization.
  Journal
J Mol Neurosci 40:154-63 (2010)
DOI:10.1007/s12031-009-9230-7
Reference
  Authors
Barik J, Wonnacott S
  Title
Molecular and cellular mechanisms of action of nicotine in the CNS.
  Journal
Handb Exp Pharmacol 173-207 (2009)
DOI:10.1007/978-3-540-69248-5_7
Reference
  Authors
Yang KC, Jin GZ, Wu J
  Title
Mysterious alpha6-containing nAChRs: function, pharmacology, and pathophysiology.
  Journal
Acta Pharmacol Sin 30:740-51 (2009)
DOI:10.1038/aps.2009.63
Reference
  Authors
Pidoplichko VI, Noguchi J, Areola OO, Liang Y, Peterson J, Zhang T, Dani JA
  Title
Nicotinic cholinergic synaptic mechanisms in the ventral tegmental area contribute to nicotine addiction.
  Journal
Learn Mem 11:60-9 (2004)
DOI:10.1101/lm.70004
Reference
  Authors
Wooltorton JR, Pidoplichko VI, Broide RS, Dani JA
  Title
Differential desensitization and distribution of nicotinic acetylcholine receptor subtypes in midbrain dopamine areas.
  Journal
J Neurosci 23:3176-85 (2003)
DOI:10.1523/JNEUROSCI.23-08-03176.2003
Reference
  Authors
Xi ZX, Spiller K, Gardner EL
  Title
Mechanism-based medication development for the treatment of nicotine dependence.
  Journal
Acta Pharmacol Sin 30:723-39 (2009)
DOI:10.1038/aps.2009.46
Reference
  Authors
Laviolette SR, van der Kooy D
  Title
The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour.
  Journal
Nat Rev Neurosci 5:55-65 (2004)
DOI:10.1038/nrn1298
Reference
  Authors
Changeux JP
  Title
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice.
  Journal
Nat Rev Neurosci 11:389-401 (2010)
DOI:10.1038/nrn2849
Reference
  Authors
Dani JA, Bertrand D
  Title
Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.
  Journal
Annu Rev Pharmacol Toxicol 47:699-729 (2007)
DOI:10.1146/annurev.pharmtox.47.120505.105214
Reference
  Authors
Mansvelder HD, Keath JR, McGehee DS
  Title
Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas.
  Journal
Neuron 33:905-19 (2002)
DOI:10.1016/S0896-6273(02)00625-6
Reference
  Authors
O'Dell LE
  Title
A psychobiological framework of the substrates that mediate nicotine use during adolescence.
  Journal
Neuropharmacology 56 Suppl 1:263-78 (2009)
DOI:10.1016/j.neuropharm.2008.07.039
Reference
  Authors
Ortells MO, Arias HR
  Title
Neuronal networks of nicotine addiction.
  Journal
Int J Biochem Cell Biol 42:1931-5 (2010)
DOI:10.1016/j.biocel.2010.08.019
Reference
  Authors
Dani JA, Harris RA
  Title
Nicotine addiction and comorbidity with alcohol abuse and mental illness.
  Journal
Nat Neurosci 8:1465-70 (2005)
DOI:10.1038/nn1580
Reference
  Authors
Markou A
  Title
Review. Neurobiology of nicotine dependence.
  Journal
Philos Trans R Soc Lond B Biol Sci 363:3159-68 (2008)
DOI:10.1098/rstb.2008.0095
Reference
  Authors
Dajas-Bailador F, Wonnacott S
  Title
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
  Journal
Trends Pharmacol Sci 25:317-24 (2004)
DOI:10.1016/j.tips.2004.04.006
Related
pathway
mna04724  Glutamatergic synapse
mna04727  GABAergic synapse
mna04728  Dopaminergic synapse
KO pathway
ko05033   
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