Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient mice.

The importance of AMPA-type glutamate receptors has been demonstrated in neuronal plasticity and in adaptation to drugs of abuse. We studied the involvement of AMPA receptors in social interaction and anxiety and found that in several paradigms of agonistic behavior naïve male mice deficient for the GluR-A subunit- containing AMPA receptors are less aggressive than wild-type littermates. GluR-A deficient mice and wild-type littermates exhibited similar basic behavior and reflexes as monitored by observational Irwin's test, but they tended to be less anxious in elevated plus-maze and light-dark tests. Maternal aggression or male-female encounters were not affected which suggests that male hormones are involved in the expression of suppressed aggressiveness. However, testosterone levels and brain monoamines can be excluded and found to be similar between GluR-A deficient and wild-type littermates. The reduced AMPA receptor levels caused by the lack of the GluR-A subunit, and measured by a 30% reduction in hippocampal [3H]-S-AMPA binding, seem to be the reason for suppressed male aggressiveness. When we analyzed mice with reduced number of functional AMPA receptors mediated by the genomic introduced GluR-A(Q582R) channel mutation, we observed again male-specific suppressed aggression, providing additional evidence for GluR-A subunit-containing AMPA receptor involvement in aggression.