Biology Reference
In-Depth Information
The FST may yield false positive results with drugs that increase
motor activity and this possibility needs to be assessed in a sepa-
rate test of drug effects on locomotor activity. Important limita-
tions of the FST include that it does not distinguish acute from
chronic antidepressant effects and therefore is not useful for
assessing time-dependent actions of antidepressants. This com-
bined with the selectivity for monoamine-based mechanisms may
limit the ability of the FST to detect novel mechanisms (
19, 20
).
Hyponeophagia paradigms are anxiety-based, and compare
feeding behavior in an anxiogenic vs. a non-anxiogenic envi-
ronment. The stress employed in these models is very mild and
consists of placing the experimental animal in a novel environ-
ment to induce anxiety during testing. The animal experiences
conflict between the desire to approach and feed or drink, and
the anxiety-induced avoidance of the novel environment.
The hyponeophagia paradigms are sensitive to acute and
chronic anxiolytic effects of benzodiazepines (
21
). They detect
anxiolytic effects of antidepressants only after chronic treatment,
which agrees with the temporal profile for this effect in humans
(
22, 23
). Utility of hyponeophagia paradigms is that they are
bidirectionally sensitive, are selective for chronic effects of anti-
depressants and have no significant training requirement.
The neural mechanisms underlying anxiety and depression may
be related as suggested by their comorbidity and the comparable
efficacy of antidepressants in the treatment of both disorders
(
24-26
). These considerations suggest that common neural sub-
strates modulate anxiety and depressive mood, and validate use of
anxiety components in animal depression models.
The novel object recognition test is a test of learning and
memory in rodents. This test is based on the tendency of a rodent
to interact with and explore a novel object to a greater extent
than with a familiar object (
27
). The degree of the difference in
novel vs. familiar object exploration is related to the strength of
the memory the animal has of the familiar object. In this test,
animals are exposed to two identical objects during a familiariza-
tion session. After a defined period of time, each animal is rein-
troduced to the test box that now contains one of the familiar
objects but also a novel object. The time spent exploring the
novel object relative to the time spent exploring the familiar
object is a measure of the memory of the familiar object. Tests of
learning and memory provide a functional measure of neural
plasticity that is likely important to the actions of antidepressant
treatments as well as to other classes of compounds including
trophic factors. Various learning and memory tests have been
useful in demonstrating improved cognitive function in humans
and in rodent models following treatment with EPO or related
compounds (
7, 28-30
).
Search WWH ::
Custom Search