Entry Name Nicotine addiction - Lemur catta (Ring-tailed lemur)
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 Lemur catta (Ring-tailed lemur) [GN:
lcat ]
Gene 123622771 CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806 ]
123624085 GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186 ]
123624805 GABRB1; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181 ]
123624857 GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175 ]
123624869 GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175 ]
123626342 CHRNA6; neuronal acetylcholine receptor subunit alpha-6 [KO:K04808 ]
123628685 GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192 ]
123628686 GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X1 [KO:K05175 ]
123628692 GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185 ]
123632367 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
123633062 GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190 ]
123633064 GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190 ]
123634030 CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813 ]
123634750 GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184 ]
123637429 CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344 ]
123637995 GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186 ]
123637997 GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175 ]
123637998 GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181 ]
123638879 GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175 ]
123639396 SLC17A8; vesicular glutamate transporter 3 isoform X1 [KO:K12302 ]
123641680 SLC17A6; vesicular glutamate transporter 2 isoform X1 [KO:K12302 ]
123642471 GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190 ]
123644398 GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186 ]
123644640 GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181 ]
123645191 GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175 ]
123645215 CHRNA7; neuronal acetylcholine receptor subunit alpha-7 [KO:K04809 ]
123646347 CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849 ]
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
