GIRK2 deficient mice - Evidence for hyperactivity and reduced anxiety

G-protein activated inwardly rectifying potassium channel (GIRK2)-deficient (null mutant) mice were examined in three tests for anxiety: the elevated plus-maze, light/dark box and "canopy" test. In the elevated plus-maze test , GIRK2 null mutant mice spent a higher percentage of time in the open arms and showed a higher number of total entries. A short (6 days) period of so cial isolation decreased anxiety and also increased the total activity in G IRK2 mutant mice. However, the increase of total activity in GIRK2 null mut ant mice was mostly due to an increase in the number of entries into the op en arms. The behavior of the wild-type animals was not substantially change d after social isolation. In the light/dark box, GIRK2 homozygous (-/-) mic e demonstrated a higher level of locomotion and a higher number of rearings in the light area. In the "canopy" test, GIRK2 mutant mice displayed an in creased locomotion in the exposed area and a strong trend to decrease in th e number of stretched attend postures (SAP) in the most secure "canopy" are a. GIRK2 heterozygous (+/-) animals showed behavioral changes intermediate between wild-type and null mutants only in the elevated plus-maze test afte r social isolation. In all other tests, GIRK2 heterozygous (+/-) animals di d not differ from wild-type mice. Taken together, this data demonstrates th at GIRK2 null mutant mice have reduced anxiety with signs of hyperactivity. We suggest that the functional block of dopamine D3 receptors may be a rea son for this phenotype. (C) 2001 Elsevier Science Inc. All rights reserved.