DBA/2Ibg mice are incapable of cholinergically-based learning in the Morris water task

In comparison to C57BL/6Ibg mice, DBA/2Ibg mice are slow to find a submerged platform in the Morris water task. Spatial learning in this task is known to be severely disrupted by treatments that reduce muscarinic cholinergic function. DBA mice were chronically treated with diisopropylfluorophosphate (DFP) in order to decrease muscarinic binding in the brain. Despite significant losses of binding sites in cortex, midbrain, hindbrain, hippocampus, and striatum, the mice failed to show an effect of DFP treatment on latency to reach the platform. Saline-treated DBA mice showed only marginal preference for searching the appropriate region of the pool during a probe trial in which the platform was absent from the pool. The pattern of search behavior was not altered by DFP treatment. These data are in strong contrast to data obtained previously with C57BL/6Ibg mice, which show accurate search behavior that is completely disrupted by DFP treatment. DBA mice thus appear incapable of true, cholinergically-mediated spatial learning. It is hypothesized that these mice lack normal function of the septo-hippocampal system.