Depression is the most common disorders of
mood rather than disturbances of thought or cognition; it may range from a very
slight condition, bordering on normality, to severe depression accompanied by
hallucinations and delusions. Worldwide, depression is a major cause of
disability and premature death. In addition to the noteworthy suicide risk,
depressed individuals are more likely to die from other causes, such as heart
disease or cancer. There are two distinct types of depressive syndrome, namely unipolar
depression, in which the mood swings are constantly in the same direction,
and bipolar affective disorder, in which depression alternates with
mania. The monoamine theory in 1965, recommends that depression results from
functionally deficient monoaminergic (noradrenalin and/or 5hydroxytryptamine)
transmission in the central nervous system
According to the WHO report, approximately
450 million people suffer from a mental or behavioral disorder and only a small
minority of the patient receives the basic treatment . This
mounts to 12.3% of the global burden of disease, and will rise to 15% by 2020.
Presently, out of a population of some 152 million the estimated number of
mentally disturbed people in Pakistan
is more than 14 million. According to World Health Organization statistics,
about 46% to 66% of women and 15% to 25% of men in Pakistan, suffer from depression
and anxiety (WHO, 2005).
Ambiguity about the biochemical
pathogenesis of depression raises the opportunity of finding new
antidepressants acting on other (non-amine-related) targets. Many different
approaches have been taken, and several compounds are in development .
Figure: 1 Mechanisms supposed to be involved in
the pathophysiology of depression 
include antagonists of neuropeptides- including CRH and substance P-as well as
compounds active on NMDA, acetylcholine and histamine receptors, and compounds
that act on the signal transduction pathways responsible for neurogenesis,
neural plasticity and apoptosis
drugs such as, selective serotonin
reuptake inhibitors (SSRI) are used to treat depression showing various side
effect i-e nausea, anxiety, drowsiness, insomnia, sexual dysfunction, serotonin
syndrome and thus, the search for a new antidepressant herb with less side
effects is deemed important.In the search for new therapeutic
products for the treatment of neurological disorders, medicinal plant research,
worldwide, has progressed constantly, demonstrating the pharmacological
effectiveness of different plant species in a variety of animal models.
synthetic drugs have been commonly used for the treatment of various
psychological disorders in developed countries, herbal medicines still remain
the widespread choice in the developing countries due to their ease of
availability, lesser side effects and lower cost. According to world health organization (WHO), it has been
estimated that about 75% of the world’s population depend entirely on
traditional medicines for the treatment of various diseases. Moreover, it has
been estimated that approximately 70,000 plant species are used in traditional
herbal medicines worldwide . The plants
reported for anti-depressant activity include Ginko biloba Linn, Magnola
officinlis Rehdher & E.H.Wilson, Mimosa pudica Linn, Curcuma
long Linn, Mimosa pudica Linn, Ociumum sanctum Linn, Withania
somnifera Dunual, Hypericum perforatum Linn, Piper methyticum
Forst, Siphocampylus verticillatus (Cham.) G.Don, Perilla frustescens
(Linn.) Britton, Rhizoma acori tatarinowii, Areca catechu Linn, Bacopa
monnieri (Linn.) Penn, Centella asiatica (Linn.) Urbab, Clitoria
ternatea Linn, Cimicifuga racemosa (Linn.), Circuma longa Linn,
Evening primrose (Oenothera spp.) oil .
Mouse as a model for depression
advantages of using mouse as a model, is their remarkable
similarity to human in genetics, anatomy and physiology. More than 95% of the
mouse genome is similar to human beings, making mouse genetic research
specifically appropriate to human disease. Other advantages of selecting mice
as a model are, cost-effectiveness, small dose in relation to body weight, easy
to handle and an accelerated breeding time, these points will definitely make
the research easily manageable for the researcher. In addition, animal models of depression are
crucial for identifying novel therapies for depression .
Behavioral tests for depression in mice
Tail suspension test (TST)
The Tail suspension test commonly
used as behavioral model for screening antidepressant activity in mice .
The animals will be hung by the tail on a plastic string 75 cm above the
surface with the help of an adhesive tape. The duration of immobility was
observed for a period of 8 minutes. Mice will be considered to be immobile when
they ceased struggling and remained floating motionless in water, making only
those movements necessary to keep their head above water. After the swimming
session, mice will be dried by a towel and returned to their housing conditions
Forced swim test (TST)
most frequently used behavioral model for screening antidepressant
effect in rodents . All mice were individually forced to swim in
open glass chamber (25 ×15 × 25cm) containing fresh water to a height of 15 cm
maintained at 26°±1°C. Each animal will show enthusiastic movement during
initial 2 min period of the test. The duration of immobility will be manually
recorded during the next 4 min of the total 6 min testing period. Mice will mbe
considered to be immobile when they ceased struggling and remained floating
motionless in water, making only those movements necessary to keep their head
above water. Following swimming session, mice will be towel dried and returned
to their housing conditions .
Light-dark test (LDT)
The apparatus consisted
of a Plexiglas box with two compartments (20 cm×20 cm each), one of which will
be illuminated with a white light while the other remained dark. Each animal
will be placed at the center of the illuminated compartment, facing one of the
dark areas. The time spent in illuminated and dark places, as well as the
number of entries in each space, will be recorded for 5 minutes .
Open field test (OFD)
test utilizes behavioral changes in rodents exposed to novel environments and
is used to confirm that the observed antidepressant effect is not due to
stimulation of general motor activity.
following parameters will be observed for 5 min10: activity in the center
(number of central squares crossed), spontaneous ambulation (number of squares
crossed at periphery) and rearing (No. of times the animal stands on the
rear paws) .
plants have played a significant role in human health care since the prehistoric
times. Herbal medicines are getting more popularity
because allopathic medicines have a lot of side effects. South Asian population
is using traditional system of medicines to treat a number of diseases.
available drugs for the treatment of depression, has shown numbers of relapses,
side effects, and drug interactions. Like, Tricyclic antidepressants causes dry
mouth, sour or metallic taste, epigastric distress, constipation, dizziness,
tachycardia, palpitations, blurred vision and urinary retention. Cardiovascular
effects include orthostatic hypotension, sinus tachycardia, and variable
prolongation of cardiac conduction times with the potential for arrhythmias,
particularly with overdoses . Due to mention drawbacks of
the available antidepressant drugs, attempts are proceeding to explore plants
with antidepressant activity. Some
important medicinal plants extracts reported as anti-depressant are:
Agapanthus campanulatus, Akebiae fructus, Albizzia
julibrissin, Ginko biloba Linn. Allium cepa,
Asparagus and Artemisia
absinthium . Appropriate
animal model is crucial for an activity to be fruitful. Most of the studies
reported for evaluation of plants antidepressant activities confirm that mouse
is the best animal model. However, more clinical studies are required for the
plants showing anti-depressant activities in animal studies, so that depression
can be treated effectively by using plants-based formulation. Medicinal plants
are widely available in Pakistan
and other countries. The widespread variety makes them attractive candidates
for further research.
Thus, there is a need to
conduct more research to explore the full potential of the alternative herbal
medicine by using mouse as animal model to confirm its activity.
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