Entry
Name
Nicotine addiction - Carlito syrichta (Philippine tarsier)
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
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Carlito syrichta (Philippine tarsier) [GN:
csyr ]
Gene
103257259 CHRNA6; neuronal acetylcholine receptor subunit alpha-6 isoform X1 [KO:K04808 ]
103251529 CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344 ]
103277373 CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806 ]
103250005 CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813 ]
103260517 GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175 ]
103262510 GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X1 [KO:K05175 ]
103262518 GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175 ]
103262519 GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175 ]
103266463 GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175 ]
103267421 GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175 ]
103249586 GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X2 [KO:K05181 ]
103267422 GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181 ]
103267553 GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181 ]
103272396 GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186 ]
103256756 GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186 ]
103249452 GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184 ]
103269295 GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185 ]
103250335 GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192 ]
103263387 GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189 ]
103252739 GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190 ]
103263699 GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190 ]
103263752 GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190 ]
103260837 CHRNA7; neuronal acetylcholine receptor subunit alpha-7 isoform X1 [KO:K04809 ]
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 pathway
KO pathway
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