Entry Name Morphine addiction
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 dependenceBRITE hierarchy
Pathway map Ortholog table Other DBs Orthology K04215 mu-type opioid receptor
K15015 solute carrier family 32 (vesicular inhibitory amino acid transporter)
K04997 potassium inwardly-rectifying channel subfamily J member 3
K05000 potassium inwardly-rectifying channel subfamily J member 6
K05002 potassium inwardly-rectifying channel subfamily J member 9
K04999 potassium inwardly-rectifying channel subfamily J member 5
K04344 voltage-dependent calcium channel P/Q type alpha-1A
K04849 voltage-dependent calcium channel N type alpha-1B
K05175 gamma-aminobutyric acid receptor subunit alpha
K05181 gamma-aminobutyric acid receptor subunit beta
K05186 gamma-aminobutyric acid receptor subunit gamma
K05184 gamma-aminobutyric acid receptor subunit delta
K05185 gamma-aminobutyric acid receptor subunit epsilon
K05192 gamma-aminobutyric acid receptor subunit theta
K05189 gamma-aminobutyric acid receptor subunit pi
K05190 gamma-aminobutyric acid receptor subunit rho
K04615 gamma-aminobutyric acid type B receptor
K04630 guanine nucleotide-binding protein G(i) subunit alpha
K04534 guanine nucleotide-binding protein G(o) subunit alpha
K04536 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538 guanine nucleotide-binding protein subunit beta-4
K04539 guanine nucleotide-binding protein subunit beta-5
K07826 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548 guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K13755 calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase [EC:3.1.4.17 ]
K18436 high affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7 [EC:3.1.4.53 ]
K18437 high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 [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 Related LinkDB All DBs
