Channelpedia

PubMed 11823889


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.2 , Kir3.2 , Slo1



Title: Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels.

Authors: Y A Blednov, M Stoffel, R Cooper, D Wallace, N Mane, R A Harris

Journal, date & volume: Psychopharmacology (Berl.), 2002 Feb , 159, 370-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11823889


Abstract
G-protein-coupled inwardly rectifying potassium channels (GIRKs) regulate synaptic transmission and neuronal firing rates. Co-localization of GIRK2 channels and dopamine receptors in the mesolimbic system suggests a role in regulation of motor activity.To explore the role of GIRK channels in the regulation of motor behavior.GIRK2 null mutant mice (knockout) were used. Locomotor activity in a mildly stressful situation was conducted either in a circular open field with video tracking or in standard mouse cages equipped with infrared sensors. Drugs were injected intraperitoneally or subcutaneously.GIRK2 knockout mice demonstrated a transient "hyperactive" behavioral phenotype with initially higher motor activity and slower habituation in a novel situation, increased levels of spontaneous locomotor activity during dark phase in their home cages, and impaired habituation in the open-field test. After habituation, GIRK2 knockout mice showed higher motor activity, which was inhibited by the D(1) receptor antagonist SCH 23390 and was more sensitive to the activating effects of the D(1) receptor partial agonist SKF 38393. In a novel environment (open-field) only the highest dose of SKF 38393 used (20 mg/kg) produced significant activation, perhaps due to a ceiling effect in GIRK2 knockout mice. SCH 23390 inhibited the basal activity levels of mice of both genotypes.Activation of the dopamine D(1)receptor in a stressful environment may be stronger in GIRK2 deficient mice, and this modified function of D(1) receptors may cause the transient hyperactive behavioral phenotype of these mice.