NDLI: Behavioral characterization of mice lacking GIRK/Kir3 channel subunits

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Behavioral characterization of mice lacking GIRK/Kir3 channel subunits

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pravetoni, M. Wickman, K.
Description	Country affiliation: United States Author Affiliation: Pravetoni M ( Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.)
Abstract	G protein-gated inwardly rectifying $K^{+}$ (GIRK/Kir3) channels mediate the postsynaptic inhibitory effects of many neurotransmitters and drugs of abuse. The lack of drugs selective for GIRK channels has hindered our ability to study their contributions to behavior. Here, we assessed the impact of GIRK subunit ablation on several behavioral endpoints. Mice were evaluated with respect to open-field motor activity and habituation, anxiety-related behavior, motor co-ordination and ataxia and operant performance. GIRK3 knockout $(^{−/−})$ mice behaved indistinguishably from wild-type mice in this panel of tests. $GIRK1^{−/−}$ mice and $GIRK2^{−/−}$ mice, however, showed elevated motor activity and delayed habituation to an open field. $GIRK2^{−/−}$ mice, and to a lesser extent $GIRK1^{−/−}$ mice, also displayed reduced anxiety-related behavior in the elevated plus maze. Both $GIRK1^{−/−}$ mice and $GIRK2^{−/−}$ mice displayed marked resistance to the ataxic effects of the $GABA_{B}$ receptor agonist baclofen in the rotarod test. All $GIRK^{−/−}$ mice were able to learn an operant task using food as the reinforcing agent. Within-session progressive ratio scheduling, however, showed elevated lever press behavior in $GIRK2^{−/−}$ mice and, to a lesser extent, in $GIRK1^{−/−}$ mice. Phenotypic differences between mice lacking GIRK1, GIRK2 and GIRK3 correlate well with the known impact of GIRK subunit ablation on neurotransmitter-gated GIRK currents, arguing that most neuronal GIRK channels contain GIRK1 and/or GIRK2. Altogether, our data suggest that GIRK channels make important contribution to a range of behaviors and may represent points of therapeutic intervention in disorders of anxiety, spasticity and reward.
File Format	HTM / HTML
ISSN	16011848
Issue Number	5
Volume Number	7
e-ISSN	1601183X
Journal	Genes, Brain and Behavior
Language	English
Publisher	Wiley
Publisher Date	2008-07-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Genetics Discipline Behavioral Sciences Behavior, Animal Physiology G Protein-coupled Inwardly-rectifying Potassium Channels Genetics Maze Learning Motor Activity Animals Anxiety Ataxia Conditioning (psychology) Exploratory Behavior Feeding Behavior Female Male Mice Mice, Inbred C57bl Mice, Knockout Comparative Study Journal Article Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Neurology Genetics Behavioral Neuroscience

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