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G protein gated potassium channels (GIRK/ Kir3) mediate the motor stimulatory effects of opiates
Author(s) -
Pravetoni Marco,
Wickman Kevin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.712.12
Subject(s) - g protein coupled inwardly rectifying potassium channel , ventral tegmental area , knockout mouse , dopamine , neuroscience , morphine , pharmacology , chemistry , opioid , inhibitory postsynaptic potential , conditioned place preference , g protein , medicine , biology , signal transduction , receptor , dopaminergic , biochemistry
Neuronal GIRK channels mediate the postsynaptic inhibitory effect of many neurotransmitters and drugs of abuse, including opioids. GIRK subunits are expressed in dopamine and GABA neurons of the VTA, a structure implicated in opioid‐induced behaviors. We measured the impact of genetic ablation of different GIRK subunits in mice on the motor stimulatory effects of morphine. While GIRK1 knockout and GIRK2 knockout mice showed higher motor activity levels than wild‐type controls, GIRK3 knockout mice showed decreased sensitivity to morphine. We next used a stereotaxic approach to probe the relevance of GIRK signaling in the VTA to the observed responses to systemic morphine. We challenged wild‐type and knockout mice with intra‐VTA administration of the MOR selective agonist DAMGO, and measured its motor inducing effects. Our findings mirrored phenotypes seen with systemic morphine administration. Differences in opioid‐induced behaviors seen in mice lacking different GIRK subunits likely relate to the differential distribution of GIRK subunits in GABA and dopamine neurons of the VTA. Our data suggest that GIRK channels in the VTA modulate the sensitivity to opiate‐induced behaviors in a subunit‐dependent manner.