Table 2.
Role of Mouse Girk Genes in Mediating the Behavioral Effects of Drugs of Abuse
| Drugs of Abuse | GIRK Genotypes | Behavioral Phenotypes | References |
|---|---|---|---|
| Ethanol | Girk2 (weaver), Girk2 (−/−) | ↓ Analgesia | Kobayashi et al. (1999); Blednov et al. (2003) |
| Girk2 (−/−) | ↓ CTA/CPP | Hill, Alva, Blednov, and Cunningham (2003) | |
| Girk2 (−/−), Girk3 (−/−) | ↓ Acute withdrawal severity | Blednov, Stoffel, Chang, and Harris (2001b); Kozell, Walter, Milner, Wickman, and Buck (2009); Herman et al. (2015) | |
| Girk2 (−/−) | ↑ Intakea | Blednov et al. (2001b) | |
| Girk3 (−/−) | ↑ Binge-like drinking | Herman et al. (2015) | |
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| |||
| Pentobarbital Zolpidem | Girk3 (−/−) | ↓ Withdrawal | Kozell et al. (2009) |
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| Cocaine | Girk2 (−/−) | ↑ Motor activity | Arora et al. (2010) |
| Girk2 (−/−), Girk3 (−/−) | ↓ Self-administration | Morgan, Carroll, Loth, Stoffel, and Wickman (2003) | |
|
| |||
| Opioids | Girk2 (weaver) | ↓ Morphine analgesia | Ikeda et al. (2000) |
| Girk1 (−/−), Girk2 (−/−) | ↓ Opioid analgesia | Blednov et al. (2003); Marker et al. (2004,2005); Mitrovic et al. (2003) | |
| Girk2/3 (−/−), Girk3 (−/−) | ↓ Opioid analgesia | Cruz et al. (2008); Marker et al. (2002); Smith et al. (2008) | |
| Girk2 (−/−) | ↑ Morphine-induced motor activity | Kotecki et al. (2015) | |
| Girk3 (−/−) | ↓ Morphine-induced motor activity | Kotecki et al. (2015) | |
| Girk2/3 (−/−) | ↓ Morphine withdrawal | Cruz et al. (2008) | |
The behavioral effects of drugs of abuse and the related Girk genes from weaver and knockout (−/−) mice are shown.
CTA, conditioned taste aversion; CPP, conditioned place preference.
a
Ethanol intake only increased when the ethanol bottles were available in the preferred location, but not when the positions were alternated daily to control for side preferences. Kotecki et al. (2015) also showed that selective ablation of Girk2 in VTA dopamine neurons increased morphine-induced motor activity, and the diminished activity in Girk3 (−/−) mice was rescued by restoring GIRK3 expression in the VTA.