Calcium-calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the major transcription factor cyclic AMP-response element binding protein (CREB), which plays a role in emotional behavior. Here, CaMKIV knockout mice (CaMKIV-/-) were tested in a battery of stress and anxiety-related behavioral tests, to determine if CaMKIV plays a role in emotional behavior. CaMKIV-/-exhibited a decrease in anxiety-like behavior in both the elevated plus maze and dark-light emergence tests when compared to wild-type mice. Both the acoustic startle response and prepulse inhibition of startle were decreased with the deletion of CaMKIV. In addition, CaMKIV-/- mice displayed a lack of stress-induced analgesia following restraint or cold swim stress. Our results demonstrate a key role for CaMKIV in anxiety and stress-related behavior.
