Behavioral tests have become important tools for the analysis of functional
effects of induced mutations in transgenic mice. However, depending on the
type of mutation and several experimental parameters. false positive or ne
gative findings may be obtained. Given the fact that molecular neurobiologi
sts now make increasing use of behavioral paradigms in their research, it i
s imperative to revisit such problems. In this review three tests. T-maze s
pontaneous alternation task (T-CAT), Context dependent fear conditioning (C
DFC). and Morris water maze (MWM) sensitive to hippocampal function, serve
as illustrative examples for the potential problems. Spontaneous alternatio
n tests are sometimes flawed because the handling procedure makes the test
dependent on fear rather than exploratory behavior leading to altered alter
nation rates independent of hippocampal function. CDFC can provide misleadi
ng results because the context test, assumed to be a configural task depend
ent on the hippocampus. may have a significant elemental, i.e. cued. compon
ent. MWM may pose problems if its visible platform task is disproportionate
ly easier for the subjects to solve than the hidden platform task. if the o
rder of administration of visible and hidden platform tasks is not counterb
alanced, or if inappropriate parameters are measured, Without attempting to
be exhaustive, this review discusses such experimental problems and gives
examples on how to avoid them. (C) 2001 Elsevier Science B.V. All rights re
served.