KEGG   PATHWAY: ggo05032
Entry
ggo05032                    Pathway                                
Name
Morphine addiction - Gorilla gorilla gorilla (western lowland gorilla)
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
Pathway map
ggo05032  Morphine addiction
ggo05032

Other DBs
GO: 0043278
Organism
Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
Gene
101149628  OPRM1; mu-type opioid receptor isoform X5 [KO:K04215]
101134223  DRD1; D(1A) dopamine receptor [KO:K04144]
101125943  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101141389  ADCY2; adenylate cyclase type 2 isoform X2 [KO:K08042] [EC:4.6.1.1]
101144031  ADCY3; adenylate cyclase type 3 isoform X4 [KO:K08043] [EC:4.6.1.1]
101125890  ADCY4; adenylate cyclase type 4 isoform X6 [KO:K08044] [EC:4.6.1.1]
101139873  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101126268  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101142672  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101145410  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
101128362  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
101147418  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101141898  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101143654  KCNJ9; G protein-activated inward rectifier potassium channel 3 isoform X1 [KO:K05002]
101150659  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
101127257  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X2 [KO:K04344]
101123776  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
101151548  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 isoform X2 [KO:K05175]
101153718  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
101133746  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
101138619  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
101138441  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
101133015  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
101150096  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X2 [KO:K05181]
101136960  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
101135864  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
101152522  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X2 [KO:K05186]
101132638  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 isoform X1 [KO:K05186]
101140865  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 isoform X1 [KO:K05186]
101125604  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
101135671  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
101138983  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
101139058  GABRP; gamma-aminobutyric acid receptor subunit PI [KO:K05189]
101124918  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
101135424  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X2 [KO:K05190]
101138347  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
101126330  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
101136130  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101125616  GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630]
101154597  GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 isoform X1 [KO:K04630]
101150695  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101154353  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101139939  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101134530  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825]
101146603  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101145049  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
109025414  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X1 [KO:K07826]
101153772  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101141949  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101138742  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 isoform X2 [KO:K04542]
109027862  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
115936218  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
101140639  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
109023336  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101148095  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
109028453  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545]
101139938  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101147632  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 isoform X2 [KO:K04347]
101139427  GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
101133147  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101139212  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
101134560  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101132215  neuroendocrine secretory protein 55 [KO:K04632]
109023045  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X2 [KO:K04632]
101148325  GRK3; G protein-coupled receptor kinase 3 isoform X1 [KO:K00910] [EC:2.7.11.15]
101140574  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
101148767  GRK4; G protein-coupled receptor kinase 4 isoform X10 [KO:K08291] [EC:2.7.11.16]
101125204  GRK6; G protein-coupled receptor kinase 6 isoform X1 [KO:K08291] [EC:2.7.11.16]
101142802  GRK5; G protein-coupled receptor kinase 5 isoform X1 [KO:K08291] [EC:2.7.11.16]
101151376  ARRB1; beta-arrestin-1 isoform X2 [KO:K04439]
101130862  ARRB2; beta-arrestin-2 isoform X3 [KO:K04439]
101124828  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101150691  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101139074  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101151469  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
101134260  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101148565  PDE1C; dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C isoform X4 [KO:K13755] [EC:3.1.4.17]
101144290  PDE1A; dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A isoform X6 [KO:K13755] [EC:3.1.4.17]
101140226  PDE1B; dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B isoform X1 [KO:K13755] [EC:3.1.4.17]
101128293  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X3 [KO:K18283] [EC:3.1.4.17]
101125638  PDE3A; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A [KO:K19021] [EC:3.1.4.17]
101149202  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
101139726  PDE4B; 3',5'-cyclic-AMP phosphodiesterase 4B isoform X2 [KO:K13293] [EC:3.1.4.53]
101136008  PDE4C; 3',5'-cyclic-AMP phosphodiesterase 4C isoform X1 [KO:K13293] [EC:3.1.4.53]
101126994  PDE4D; 3',5'-cyclic-AMP phosphodiesterase 4D isoform X3 [KO:K13293] [EC:3.1.4.53]
101141144  PDE7B; 3',5'-cyclic-AMP phosphodiesterase 7B isoform X2 [KO:K18436] [EC:3.1.4.53]
109023025  PDE7A; high affinity 3',5'-cyclic-AMP phosphodiesterase 7A isoform X1 [KO:K18436] [EC:3.1.4.53]
101149020  PDE8B; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B isoform X6 [KO:K18437] [EC:3.1.4.53]
101124565  PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1 [KO:K18437] [EC:3.1.4.53]
101150404  PDE11A; dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A [KO:K13298] [EC:3.1.4.17 3.1.4.35]
101140567  ADORA1; adenosine receptor A1 isoform X1 [KO:K04265]
Compound
C00020  AMP
C00076  Calcium cation
C00212  Adenosine
C00238  Potassium cation
C00334  4-Aminobutanoate
C00575  3',5'-Cyclic AMP
C00698  Cl-
C03758  Dopamine
D00842  Morphine sulfate (USP)
D02271  Morphine hydrochloride hydrate (JP18)
D08233  Morphine (BAN)
D08234  Morphine tartrate
Reference
PMID:15661627
  Authors
Bailey CP, Connor M
  Title
Opioids: cellular mechanisms of tolerance and physical dependence.
  Journal
Curr Opin Pharmacol 5:60-8 (2005)
DOI:10.1016/j.coph.2004.08.012
Reference
PMID:11152760
  Authors
Williams JT, Christie MJ, Manzoni O
  Title
Cellular and synaptic adaptations mediating opioid dependence.
  Journal
Physiol Rev 81:299-343 (2001)
DOI:10.1152/physrev.2001.81.1.299
Reference
PMID:16581089
  Authors
Gintzler AR, Chakrabarti S
  Title
Post-opioid receptor adaptations to chronic morphine; altered functionality and associations of signaling molecules.
  Journal
Life Sci 79:717-22 (2006)
DOI:10.1016/j.lfs.2006.02.016
Reference
PMID:8785060
  Authors
Bonci A, Williams JT
  Title
A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine.
  Journal
Neuron 16:631-9 (1996)
DOI:10.1016/S0896-6273(00)80082-3
Reference
PMID:11750924
  Authors
Liu JG, Anand KJ
  Title
Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence.
  Journal
Brain Res Brain Res Rev 38:1-19 (2001)
DOI:10.1016/S0165-0173(01)00057-1
Reference
PMID:10066284
  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
J Neurosci 19:2347-55 (1999)
DOI:10.1523/JNEUROSCI.19-06-02347.1999
Reference
PMID:18349442
  Authors
Zhang Y, Chen Q, Yu LC
  Title
Morphine: a protective or destructive role in neurons?
  Journal
Neuroscientist 14:561-70 (2008)
DOI:10.1177/1073858408314434
Reference
PMID:12859419
  Authors
Tso PH, Wong YH
  Title
Molecular basis of opioid dependence: role of signal regulation by G-proteins.
  Journal
Clin Exp Pharmacol Physiol 30:307-16 (2003)
DOI:10.1046/j.1440-1681.2003.03835.x
Reference
PMID:1346804
  Authors
Johnson SW, North RA
  Title
Opioids excite dopamine neurons by hyperpolarization of local interneurons.
  Journal
J Neurosci 12:483-8 (1992)
DOI:10.1523/JNEUROSCI.12-02-00483.1992
Reference
PMID:20962224
  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
J Neurosci 30:14029-35 (2010)
DOI:10.1523/JNEUROSCI.3366-10.2010
Reference
PMID:8987801
  Authors
Bonci A, Williams JT
  Title
Increased probability of GABA release during withdrawal from morphine.
  Journal
J Neurosci 17:796-803 (1997)
DOI:10.1523/JNEUROSCI.17-02-00796.1997
Reference
PMID:21872647
  Authors
Morikawa H, Paladini CA
  Title
Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms.
  Journal
Neuroscience 198:95-111 (2011)
DOI:10.1016/j.neuroscience.2011.08.023
Reference
PMID:12217944
  Authors
Xi ZX, Stein EA
  Title
GABAergic mechanisms of opiate reinforcement .
  Journal
Alcohol Alcohol 37:485-94 (2002)
DOI:10.1093/alcalc/37.5.485
Reference
PMID:8096779
  Authors
Kalivas PW
  Title
Neurotransmitter regulation of dopamine neurons in the ventral tegmental area.
  Journal
Brain Res Brain Res Rev 18:75-113 (1993)
DOI:10.1016/0165-0173(93)90008-N
Reference
PMID:21930931
  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
Proc Natl Acad Sci U S A 108:16446-50 (2011)
DOI:10.1073/pnas.1105418108
Reference
PMID:14625081
  Authors
Chakrabarti S, Gintzler AR
  Title
Phosphorylation of Gbeta is augmented by chronic morphine and enhances Gbetagamma stimulation of adenylyl cyclase activity.
  Journal
Brain Res Mol Brain Res 119:144-51 (2003)
DOI:10.1016/j.molbrainres.2003.09.002
Reference
PMID:14969742
  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
Brain Res Mol Brain Res 121:114-22 (2004)
DOI:10.1016/j.molbrainres.2003.11.009
Related
pathway
ggo04727  GABAergic synapse
ggo04728  Dopaminergic synapse
KO pathway
ko05032   
LinkDB

DBGET integrated database retrieval system