Abstract:
Reactivity to environmental stressors influences
vulnerability to neurological and psychiatric illnesses, but
little is known about molecular mechanisms that control this
reactivity. Since mice with forebrain-specific glucocorticoid
receptor overexpression (GRov mice) display anxiety-like behaviors
in novel environments and have difficulty adjusting
to change in memory tasks, we hypothesized that these may
be facets of a broader phenotype of altered reactivity to
environmental demands. Male GRov and wild-type mice were
tested in a multiple-trial object interaction test comprising
environmental and object habituation and spatial and object
novelty trials. Half the mice received restraint stress before
testing. GRov mice exhibited more locomotor activity and,
without stress, more object interaction than wild-type mice.
Following acute stress, GRov mice no longer showed increased
object exploration. While stress dampened responses
to object novelty in both groups, GRov mice were
particularly impaired in discrimination of spatial novelty poststress.
These data demonstrate that GRov leads to increased
environmental reactivity, responsiveness to salience, and
vulnerability to stress-induced cognitive deficits. They implicate
forebrain glucocorticoid receptor (GR) in fine-tuning interactions
with the environment and the interplay of emotional
salience, coping abilities, and cognitive function.
