Entry |
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Name |
Morphine addiction - Loxodonta africana (African savanna elephant)
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Description |
Morphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most important brain-reward circuit involves dopamine (DA) -containing neurons in the ventral tegmental area (VTA) of the midbrain and their target areas in the limbic forebrain, in particular, the nucleus accumbens (NAc) and frontal regions of cerebral cortex. Morphine can cause indirect excitation of VTA dopamine neurons by reducing inhibitory synaptic transmission mediated by GABAergic neurons. The chronic use of morphine is characterized by adaptive changes in neurons and neuronal communication; such adaptations (e.g., 'superactivation' of adenylyl cyclase) must underlie altered behaviour associated with morphine dependence and withdrawal syndrome, as well as drug-induced craving and relapse to drug use.
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Class |
Human Diseases; Substance dependence
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Pathway map |

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Other DBs |
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Organism |
Loxodonta africana (African savanna elephant) [GN: lav]
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Gene |
100653936 | SLC32A1; LOW QUALITY PROTEIN: vesicular inhibitory amino acid transporter [KO:K15015] |
100668323 | KCNJ3; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 1 [KO:K04997] |
100676455 | KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000] |
100655762 | KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999] |
100655176 | CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344] |
100660444 | CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849] |
100659390 | GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175] |
100659678 | GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175] |
100673112 | GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175] |
100665743 | GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175] |
100662419 | GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175] |
100666647 | GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175] |
100658920 | GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181] |
100673796 | GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181] |
100662142 | GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181] |
100659961 | GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186] |
100666363 | GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186] |
100662697 | GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186] |
100676800 | GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184] |
100670286 | GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185] |
100666025 | GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192] |
100670099 | GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190] |
100670389 | GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X2 [KO:K05190] |
100665222 | GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190] |
100657108 | GABBR1; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615] |
100657997 | GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615] |
100666344 | GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630] |
100670234 | GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630] |
100667957 | GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630] |
100658419 | GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534] |
100673391 | GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536] |
100677127 | GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537] |
100674807 | GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825] |
100669106 | GNB4; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit beta-4 [KO:K04538] |
100674665 | GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539] |
100668996 | GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X2 [KO:K07826] |
100676083 | GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540] |
100664179 | GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541] |
100656403 | GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542] |
100655407 | GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543] |
100662559 | GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545] |
111749727 | GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546] |
111751488 | GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347] |
111750996 | GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347] |
100675882 | GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547] |
111749728 | GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548] |
111751775 | GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549] |
100655206 | guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632] |
100677239 | PDE1B; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B isoform X2 [KO:K13755] [EC:3.1.4.17] |
100674025 | PDE1A; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A isoform X1 [KO:K13755] [EC:3.1.4.17] |
100674033 | PDE1C; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C isoform X1 [KO:K13755] [EC:3.1.4.17] |
100673758 | PDE7A; high affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A isoform X1 [KO:K18436] [EC:3.1.4.53] |
100670699 | PDE8B; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B [KO:K18437] [EC:3.1.4.53] |
100658501 | PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X3 [KO:K18437] [EC:3.1.4.53] |
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Compound |
D02271 | Morphine hydrochloride hydrate (JP17) |
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Reference |
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Authors |
Bailey CP, Connor M |
Title |
Opioids: cellular mechanisms of tolerance and physical dependence. |
Journal |
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Reference |
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Authors |
Williams JT, Christie MJ, Manzoni O |
Title |
Cellular and synaptic adaptations mediating opioid dependence. |
Journal |
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Reference |
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Authors |
Gintzler AR, Chakrabarti S |
Title |
Post-opioid receptor adaptations to chronic morphine; altered functionality and associations of signaling molecules. |
Journal |
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Reference |
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Authors |
Bonci A, Williams JT |
Title |
A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine. |
Journal |
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Reference |
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Authors |
Liu JG, Anand KJ |
Title |
Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence. |
Journal |
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Reference |
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Authors |
Shoji Y, Delfs J, Williams JT |
Title |
Presynaptic inhibition of GABA(B)-mediated synaptic potentials in the ventral tegmental area during morphine withdrawal. |
Journal |
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Reference |
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Authors |
Zhang Y, Chen Q, Yu LC |
Title |
Morphine: a protective or destructive role in neurons? |
Journal |
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Reference |
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Authors |
Tso PH, Wong YH |
Title |
Molecular basis of opioid dependence: role of signal regulation by G-proteins. |
Journal |
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Reference |
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Authors |
Johnson SW, North RA |
Title |
Opioids excite dopamine neurons by hyperpolarization of local interneurons. |
Journal |
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Reference |
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Authors |
Madhavan A, Bonci A, Whistler JL |
Title |
Opioid-Induced GABA potentiation after chronic morphine attenuates the rewarding effects of opioids in the ventral tegmental area. |
Journal |
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Reference |
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Authors |
Bonci A, Williams JT |
Title |
Increased probability of GABA release during withdrawal from morphine. |
Journal |
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Reference |
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Authors |
Morikawa H, Paladini CA |
Title |
Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms. |
Journal |
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Reference |
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Authors |
Xi ZX, Stein EA |
Title |
GABAergic mechanisms of opiate reinforcement . |
Journal |
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Reference |
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Authors |
Kalivas PW |
Title |
Neurotransmitter regulation of dopamine neurons in the ventral tegmental area. |
Journal |
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Reference |
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Authors |
Jalabert M, Bourdy R, Courtin J, Veinante P, Manzoni OJ, Barrot M, Georges F |
Title |
Neuronal circuits underlying acute morphine action on dopamine neurons. |
Journal |
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Reference |
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Authors |
Chakrabarti S, Gintzler AR |
Title |
Phosphorylation of Gbeta is augmented by chronic morphine and enhances Gbetagamma stimulation of adenylyl cyclase activity. |
Journal |
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Reference |
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Authors |
Ferrer-Alcon M, La Harpe R, Garcia-Sevilla JA |
Title |
Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and beta-arrestin-2 in postmortem brains of opiate addicts. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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