Entry Name Nicotine addiction
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 Orthology K04344 CACNA1A, CAV2.1; voltage-dependent calcium channel P/Q type alpha-1A
K04806 CHRNA4; nicotinic acetylcholine receptor alpha-4
K04808 CHRNA6; nicotinic acetylcholine receptor alpha-6
K04809 CHRNA7; nicotinic acetylcholine receptor alpha-7
K04813 CHRNB2; nicotinic acetylcholine receptor beta-2
K04849 CACNA1B, CAV2.2; voltage-dependent calcium channel N type alpha-1B
K05175 GABRA; gamma-aminobutyric acid receptor subunit alpha
K05181 GABRB; gamma-aminobutyric acid receptor subunit beta
K05184 GABRD; gamma-aminobutyric acid receptor subunit delta
K05185 GABRE; gamma-aminobutyric acid receptor subunit epsilon
K05186 GABRG; gamma-aminobutyric acid receptor subunit gamma
K05189 GABRP; gamma-aminobutyric acid receptor subunit pi
K05190 GABRR; gamma-aminobutyric acid receptor subunit rho
K05192 GABRQ; gamma-aminobutyric acid receptor subunit theta
K05197 GRIA1; glutamate receptor 1
K05198 GRIA2; glutamate receptor 2
K05199 GRIA3; glutamate receptor 3
K05200 GRIA4; glutamate receptor 4
K05208 GRIN1; glutamate receptor ionotropic, NMDA 1
K05209 GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210 GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05211 GRIN2C; glutamate receptor ionotropic, NMDA 2C
K05212 GRIN2D; glutamate receptor ionotropic, NMDA 2D
K05213 GRIN3A; glutamate receptor ionotropic, NMDA 3A
K05214 GRIN3B; glutamate receptor ionotropic, NMDA 3B
K12302 SLC17A6_7_8; MFS transporter, ACS family, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6/7/8
K15015 SLC32A, VGAT; solute carrier family 32 (vesicular inhibitory amino acid transporter)
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
