Alterations in the levels of heterotrimeric G protein subunits induced by psychostimulants, opiates, barbiturates, and ethanol: Implications for drug dependence, tolerance, and withdrawal.
Neuronal adaptations have been found to occur in multiple brain regions after chronic intake of abused drugs, and are therefore thought to underlie drug dependence, tolerance, and withdrawal. Pathophysiological changes in drug responsiveness as well as behavioral sequelae of chronic drug exposure are thought to depend largely upon the altered state of heterotrimeric GTP binding protein (G protein)-coupled receptor (GPCR)-G protein interactions. Responsiveness of GPCR-related intracellular signaling systems to drugs of abuse is heterogeneous, depending on the types of intracellular effectors to which the specific Galpha protein subtypes are coupled and GPCR-G protein coupling efficiency, factors influenced by the class of drug, expression levels of G protein subunits, and drug treatment regimens. To enhance understanding of the molecular mechanisms that underlie the development of pathophysiological states resulting from chronic intake of abused drugs, this review focuses on alterations in the expression levels of G protein subunits induced by various drugs of abuse. Changes in these mechanisms appear to be specific to particular drugs of abuse, and specific conditions of drug treatment.
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan. kitanaka-hyg@umin.net
Nobue
N
Kitanaka
Junichi
J
Kitanaka
F Scott
FS
Hall
Tomohiro
T
Tatsuta
Yoshio
Y
Morita
Motohiko
M
Takemura
Xiao-Bing
XB
Wang
George R
GR
Uhl
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004361:Drug Tolerance / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*
D000701:Analgesics, Opioid; D001463:Barbiturates; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D000431:Ethanol; D020962:Heterotrimeric GTP-Binding Proteins