Entry
Name
Morphine addiction - Odobenus rosmarus divergens (Pacific walrus)
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.
Class
Human Diseases; Substance dependence
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:
oro ]
Gene
101383826 KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997 ]
101366647 KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000 ]
101378770 KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002 ]
101370849 KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999 ]
101378448 CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344 ]
105758129 voltage-dependent N-type calcium channel subunit alpha-1B-like [KO:K04849 ]
101367195 GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175 ]
101367694 GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175 ]
101383169 GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175 ]
101384124 GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175 ]
101384663 GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175 ]
101374508 GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 isoform X2 [KO:K05175 ]
101375620 GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181 ]
101367987 GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181 ]
101382692 GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X2 [KO:K05181 ]
101366419 GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186 ]
101374799 GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186 ]
101384321 GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186 ]
101381192 GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184 ]
101373634 GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185 ]
101376482 GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192 ]
101381014 GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189 ]
101362961 GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190 ]
101371998 GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190 ]
101372494 GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190 ]
101374451 GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615 ]
101378598 GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615 ]
101376186 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630 ]
101367568 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
101367936 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
101376297 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
101381482 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 isoform X1 [KO:K04536 ]
101378633 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537 ]
101371845 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
101369300 GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
101362117 GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539 ]
101366315 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
101376879 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
101369684 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
101365462 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
101363588 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
101371482 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
101370001 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
101375712 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
101379027 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
101374080 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
101368814 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04347 ]
101382152 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
101375999 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 isoform X1 [KO:K04548 ]
101386155 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
101364060 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
101365244 PDE1A; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A isoform X1 [KO:K13755 ] [EC:3.1.4.17 ]
101380225 PDE1B; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B [KO:K13755 ] [EC:3.1.4.17 ]
101363002 PDE1C; calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C isoform X1 [KO:K13755 ] [EC:3.1.4.17 ]
101367755 PDE7A; high affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A isoform X1 [KO:K18436 ] [EC:3.1.4.53 ]
101367637 PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1 [KO:K18437 ] [EC:3.1.4.53 ]
101377436 PDE8B; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B isoform X1 [KO:K18437 ] [EC:3.1.4.53 ]
Compound
D02271 Morphine hydrochloride hydrate (JP18)
Reference
Authors
Bailey CP, Connor M
Title
Opioids: cellular mechanisms of tolerance and physical dependence.
Journal
Reference
Authors
Williams JT, Christie MJ, Manzoni O
Title
Cellular and synaptic adaptations mediating opioid dependence.
Journal
Reference
Authors
Gintzler AR, Chakrabarti S
Title
Post-opioid receptor adaptations to chronic morphine; altered functionality and associations of signaling molecules.
Journal
Reference
Authors
Bonci A, Williams JT
Title
A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine.
Journal
Reference
Authors
Liu JG, Anand KJ
Title
Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence.
Journal
Reference
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
Reference
Authors
Zhang Y, Chen Q, Yu LC
Title
Morphine: a protective or destructive role in neurons?
Journal
Reference
Authors
Tso PH, Wong YH
Title
Molecular basis of opioid dependence: role of signal regulation by G-proteins.
Journal
Reference
Authors
Johnson SW, North RA
Title
Opioids excite dopamine neurons by hyperpolarization of local interneurons.
Journal
Reference
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
Reference
Authors
Bonci A, Williams JT
Title
Increased probability of GABA release during withdrawal from morphine.
Journal
Reference
Authors
Morikawa H, Paladini CA
Title
Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms.
Journal
Reference
Authors
Xi ZX, Stein EA
Title
GABAergic mechanisms of opiate reinforcement .
Journal
Reference
Authors
Kalivas PW
Title
Neurotransmitter regulation of dopamine neurons in the ventral tegmental area.
Journal
Reference
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
Reference
Authors
Chakrabarti S, Gintzler AR
Title
Phosphorylation of Gbeta is augmented by chronic morphine and enhances Gbetagamma stimulation of adenylyl cyclase activity.
Journal
Reference
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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