2017
DOI: 10.1016/j.tips.2017.01.007
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G Protein-Gated Potassium Channels: A Link to Drug Addiction

Abstract: G protein-gated inwardly rectifying potassium (GIRK) channels are regulators of neuronal excitability in the brain. Knockout mice lacking GIRK channels display altered behavioral responses to multiple addictive drugs, implicating GIRK channels in addictive behaviors. Here, we review the effects of GIRK subunit deletions on the behavioral response to psychostimulants, such as cocaine and methamphetamine. Additionally, exposure of mice to psychostimulants produces alterations in surface expression of GIRK channe… Show more

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Cited by 46 publications
(38 citation statements)
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References 100 publications
(172 reference statements)
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“…VTA DA neurons express solely GIRK2c and GIRK3 (Cruz et al, 2004). GIRKs control the excitability of VTA DA neurons by hyperpolarizing neurons when activated and thus preventing AP generation (Rifkin, Moss, & Slesinger, 2017). The activation/inactivation of GIRKs has been shown to be modulated by the phosphorylation of PKA (Rusinova et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…VTA DA neurons express solely GIRK2c and GIRK3 (Cruz et al, 2004). GIRKs control the excitability of VTA DA neurons by hyperpolarizing neurons when activated and thus preventing AP generation (Rifkin, Moss, & Slesinger, 2017). The activation/inactivation of GIRKs has been shown to be modulated by the phosphorylation of PKA (Rusinova et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…The strength of GIRK channel activity in VTA DA neurons is also modulated by neuronal excitability, with large depolarization events (e.g., phasic DA neuron firing) potentiating GIRK-dependent signaling, and hyperpolarization or tonic DA neuron firing reducing GIRK-dependent signaling (Lalive et al, 2014). These observations converge on a working model wherein in vivo psychostimulant exposure inhibits DA neurons via GABA B R and D 2 R activation, leading to decreased strength of inhibitory G protein signaling mediated by GIRK channel activation and, consequently, increased behavioral sensitivity to cocaine (Hearing et al, 2012;Marron Fernandez de Velasco et al, 2015;Rifkin et al, 2017).…”
Section: Introductionmentioning
confidence: 98%
“…Inwardly rectifying potassium channels are activated by neurotransmitters and hormones as well as by other messengers such as kinases and G-proteins (Dascal, 1997). The G protein-activated potassium (GIRK) channels can be directly activated by ethanol (Aryal et al , 2009) and have been found to play a role in drug addiction (Herman et al , 2015; McCall et al , 2016; Munoz et al , 2016; Rifkin et al , 2017). Here we show that ethanol-induced CPP increases the excitability of vBNST neurons by potentially blocking inwardly-rectifying potassium channels.…”
Section: Discussionmentioning
confidence: 99%