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 social isolation decreased anxiety and also increased the total activity in GIRK2 mutant mice. However, the increase of total activity in GIRK2 null mutant mice was mostly due to an increase in the number of entries into the open arms. The behavior of the wild-type animals was not substantially changed after social isolation. In the light/dark box, GIRK2 homozygous (-/-) mice 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 increased locomotion in the exposed area and a strong trend to decrease in the number of stretched attend postures (SAP) in the most secure "canopy" area. GIRK2 heterozygous (+/-) animals showed behavioral changes intermediate between wild-type and null mutants only in the elevated plus-maze test after social isolation. In all other tests, GIRK2 heterozygous (+/-) animals did not differ from wild-type mice. Taken together, this data demonstrates that GIRK2 null mutant mice have reduced anxiety with signs of hyperactivity. We suggest that the functional block of dopamine D3 receptors may be a reason for this phenotype.