TY - CHAP
T1 - GABAB Receptors and Drug Addiction
T2 - Psychostimulants and Other Drugs of Abuse
AU - Li, Xiaofan
AU - Slesinger, Paul A.
N1 - Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2022
Y1 - 2022
N2 - Metabotropic GABAB receptors (GABABRs) mediate slow inhibition and modulate synaptic plasticity throughout the brain. Dysfunction of GABABRs has been associated with psychiatric illnesses and addiction. Drugs of abuse alter GABAB receptor (GABABR) signaling in multiple brain regions, which partly contributes to the development of drug addiction. Recently, GABABR ligands and positive allosteric modulators (PAMs) have been shown to attenuate the initial rewarding effect of addictive substances, inhibit seeking and taking of these drugs, and in some cases, ameliorate drug withdrawal symptoms. The majority of the anti-addiction effects seen with GABABR modulation can be localized to ventral tegmental area (VTA) dopamine neurons, which receive complex inhibitory and excitatory inputs that are modified by drugs of abuse. Preclinical research suggests that GABABR PAMs are emerging as promising candidates for the treatment of drug addiction. Clinical studies on drug dependence have shown positive results with GABABR ligands but more are needed, and compounds with better pharmacokinetics and fewer side effects are critically needed.
AB - Metabotropic GABAB receptors (GABABRs) mediate slow inhibition and modulate synaptic plasticity throughout the brain. Dysfunction of GABABRs has been associated with psychiatric illnesses and addiction. Drugs of abuse alter GABAB receptor (GABABR) signaling in multiple brain regions, which partly contributes to the development of drug addiction. Recently, GABABR ligands and positive allosteric modulators (PAMs) have been shown to attenuate the initial rewarding effect of addictive substances, inhibit seeking and taking of these drugs, and in some cases, ameliorate drug withdrawal symptoms. The majority of the anti-addiction effects seen with GABABR modulation can be localized to ventral tegmental area (VTA) dopamine neurons, which receive complex inhibitory and excitatory inputs that are modified by drugs of abuse. Preclinical research suggests that GABABR PAMs are emerging as promising candidates for the treatment of drug addiction. Clinical studies on drug dependence have shown positive results with GABABR ligands but more are needed, and compounds with better pharmacokinetics and fewer side effects are critically needed.
KW - Dopamine
KW - Positive allosteric modulators (PAMs)
KW - Synaptic plasticity
KW - Ventral tegmental area (VTA)
UR - http://www.scopus.com/inward/record.url?scp=85122381405&partnerID=8YFLogxK
U2 - 10.1007/7854_2020_187
DO - 10.1007/7854_2020_187
M3 - Chapter
C2 - 33442842
AN - SCOPUS:85122381405
T3 - Current Topics in Behavioral Neurosciences
SP - 119
EP - 155
BT - Current Topics in Behavioral Neurosciences
PB - Springer Science and Business Media Deutschland GmbH
ER -