Entry Name Nicotine addiction - Miniopterus natalensis (Natal long-fingered bat)
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 dependenceBRITE hierarchy
Pathway map Other DBs Organism Miniopterus natalensis (Natal long-fingered bat) [GN:
mna ]
Gene 107523942 CHRNA6; neuronal acetylcholine receptor subunit alpha-6 [KO:K04808 ]
107525462 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
107527103 GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190 ]
107527855 GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186 ]
107527865 GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175 ]
107528034 GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181 ]
107529071 CHRNA4; neuronal acetylcholine receptor subunit alpha-4 isoform X1 [KO:K04806 ]
107532484 GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 isoform X1 [KO:K05186 ]
107532500 GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175 ]
107533097 GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175 ]
107533104 GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181 ]
107533430 GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190 ]
107533431 GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190 ]
107534564 GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214 ]
107536136 CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849 ]
107536149 GRIN1; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 1 [KO:K05208 ]
107537858 GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175 ]
107537863 GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186 ]
107537880 GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181 ]
107537889 GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175 ]
107537964 GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192 ]
107537965 GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X1 [KO:K05175 ]
107540159 GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184 ]
107541038 CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344 ]
107543725 CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813 ]
107545115 SLC17A8; vesicular glutamate transporter 3 isoform X1 [KO:K12302 ]
Compound Reference Authors Mansvelder HD, McGehee DS
Title Cellular and synaptic mechanisms of nicotine addiction.
Journal Reference Authors Wonnacott S, Sidhpura N, Balfour DJ
Title Nicotine: from molecular mechanisms to behaviour.
Journal Reference Authors Mao D, McGehee DS
Title Nicotine and behavioral sensitization.
Journal Reference Authors Barik J, Wonnacott S
Title Molecular and cellular mechanisms of action of nicotine in the CNS.
Journal Reference Authors Yang KC, Jin GZ, Wu J
Title Mysterious alpha6-containing nAChRs: function, pharmacology, and pathophysiology.
Journal 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 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 Reference Authors Xi ZX, Spiller K, Gardner EL
Title Mechanism-based medication development for the treatment of nicotine dependence.
Journal Reference Authors Laviolette SR, van der Kooy D
Title The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour.
Journal Reference Authors Changeux JP
Title Nicotine addiction and nicotinic receptors: lessons from genetically modified mice.
Journal Reference Authors Dani JA, Bertrand D
Title Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system.
Journal Reference Authors Mansvelder HD, Keath JR, McGehee DS
Title Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas.
Journal Reference Authors O'Dell LE
Title A psychobiological framework of the substrates that mediate nicotine use during adolescence.
Journal Reference Authors Ortells MO, Arias HR
Title Neuronal networks of nicotine addiction.
Journal Reference Authors Dani JA, Harris RA
Title Nicotine addiction and comorbidity with alcohol abuse and mental illness.
Journal Reference Authors Markou A
Title Review. Neurobiology of nicotine dependence.
Journal Reference Authors Dajas-Bailador F, Wonnacott S
Title Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
Journal Related KO pathway
