Entry
Name
Morphine addiction - Chlorocebus sabaeus (green monkey)
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
Chlorocebus sabaeus (green monkey) [GN:
csab ]
Gene
103217112 KCNJ3; potassium voltage-gated channel subfamily J member 3 [KO:K04997 ]
103218752 KCNJ6; potassium voltage-gated channel subfamily J member 6 [KO:K05000 ]
103223740 KCNJ9; potassium voltage-gated channel subfamily J member 9 [KO:K05002 ]
103248811 KCNJ5; potassium voltage-gated channel subfamily J member 5 [KO:K04999 ]
103234371 CACNA1A; calcium voltage-gated channel subunit alpha1 A [KO:K04344 ]
103239541 CACNA1B; calcium voltage-gated channel subunit alpha1 B [KO:K04849 ]
103232759 GABRA3; gamma-aminobutyric acid type A receptor alpha3 subunit [KO:K05175 ]
103244913 GABRA1; gamma-aminobutyric acid type A receptor alpha1 subunit [KO:K05175 ]
103244915 GABRA6; gamma-aminobutyric acid type A receptor alpha6 subunit [KO:K05175 ]
103246006 GABRA5; gamma-aminobutyric acid type A receptor alpha5 subunit [KO:K05175 ]
103246143 GABRA4; gamma-aminobutyric acid type A receptor alpha4 subunit [KO:K05175 ]
103246148 GABRA2; gamma-aminobutyric acid type A receptor alpha2 subunit [KO:K05175 ]
103246008 GABRB3; gamma-aminobutyric acid type A receptor beta3 subunit [KO:K05181 ]
103244912 GABRB2; gamma-aminobutyric acid type A receptor beta2 subunit [KO:K05181 ]
103246145 GABRB1; gamma-aminobutyric acid type A receptor beta1 subunit [KO:K05181 ]
103244917 GABRG2; gamma-aminobutyric acid type A receptor gamma2 subunit [KO:K05186 ]
103246004 GABRG3; gamma-aminobutyric acid type A receptor gamma3 subunit [KO:K05186 ]
103246149 GABRG1; gamma-aminobutyric acid type A receptor gamma1 subunit [KO:K05186 ]
103225775 GABRD; gamma-aminobutyric acid type A receptor delta subunit [KO:K05184 ]
103232754 GABRE; gamma-aminobutyric acid type A receptor epsilon subunit [KO:K05185 ]
103232761 GABRQ; gamma-aminobutyric acid type A receptor theta subunit [KO:K05192 ]
103244961 GABRP; gamma-aminobutyric acid type A receptor pi subunit [KO:K05189 ]
103228486 GABRR3; gamma-aminobutyric acid type A receptor rho3 subunit [KO:K05190 ]
103240098 GABRR1; gamma-aminobutyric acid type A receptor rho1 subunit [KO:K05190 ]
103240100 GABRR2; gamma-aminobutyric acid type A receptor rho2 subunit [KO:K05190 ]
103219146 GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615 ]
103221881 GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615 ]
103226542 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
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
Related pathway
KO pathway
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