1. IN VIVO MODEL OF
DEPRESSION
Umangi Chauhan
NIPERA1214PC05
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2. DEPRESSION
 Depression is defined as disorders of mood rather than
disturbances of thought or cognition; it may range from a
very mild condition, bordering on normality, to severe
(psychotic) depression accompanied by hallucinations and
delusions.
 Worldwide, depression is a major cause of disability and
premature death.
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3. SYMPTOMS
 Emotional symptoms:
 misery, apathy and pessimism
 low self-esteem: feelings of guilt, inadequacy and ugliness
 indecisiveness, loss of motivation
 Biological symptoms:
 retardation of thought and action
 loss of libido
 sleep disturbance and loss of appetite
TYPES
o Unipolar depression
o Bipolar depression 3

4. THEORIES OF DEPRESSION
1. Monoamine theory:
• Monoamine hypothesis, proposed by Schildkraut in 1965,
which states that depression is caused by a functional
deficit of monoamine transmitters at certain sites in the
brain, while mania results from a functional excess i.e.
NA,5-HT.
2. Neuroendocrine mechanism:
• Increase cortisol, growth hormone concentration is
reduced and prolactin is increased.
• But these changes are nonspecific.
3. Neuroplasticity:
• Depression is associated with neuronal loss in the
hippocampus and prefrontal cortex.
• Antidepressant therapies of different kinds act by
inhibiting or actually reversing this loss by stimulating
neurogenesis.
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5. ANIMAL MODELS OF DEPRESSION
 Despair swim test
 Tail suspension test in mice
 Learned helplessness in rats
 Muricide behaviour in rats
 Potentiation of norepinephrine toxicity
 Reserpine induced hypothermia
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6. DESPAIR SWIM TEST
 Mice or rats forced to swim in a restricted space from which they
cannot escape are induced to a characteristic behavior of
immobility.
 Method:
 Rats placed in the cylinders for the first time
 Initially-They are highly active
 After 2-3 min-Starting of immobility or floating
 After 5-6 min-Remain immobile
 Test drugs or standard are administered one hour prior to
testing.
 Evaluation
 Duration of immobility is measured in controls and animals
treated with various doses of a test drug or standard.
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7. TAIL SUSPENSION TEST IN MICE
 The immobility displayed by rodents when subjected to an
unavoidable and inescapable stress has been reflect
depressive disorders in humans.
 Method
 Male Balb/cJ mice weighing 20–25 g are used
 Animals are treated with the test compounds or the
vehicle by i.p. injection 30 min prior to testing.
 Mice are suspended on the edge of a shelf 58 cm above a
table top by adhesive tape placed approximately 1 cm
from the tip of the tail.
 The duration of immobility is recorded for a period of 5
min.
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8.  Evaluation
 The percentage of animals showing the passive behavior is
counted and compared with vehicle treated controls.
 Using various doses, ED50 values can be calculated.
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9. LEARNED HELPLESSNESS IN RATS
 Animals exposed to inescapable and unavoidable electric
shocks in one situation later fail to escape shock in a
different situation when escape is possible
 Method
 Learned helplessness is produced in male Sprague-
Dawley rats (300 g) by exposure to electric shock (0.7 mA)
for 1 h on a schedule of 10 s of shock/min.
 The platform is not available during training.
 After giving test drug,the shock is initiated (0.4 mA)
 Shock is terminated in 10 s if the animal has not escaped
onto the platform by this time.
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10.  If an escape response occurred, the animal is allowed to
remain on the platform for the duration of 10 s, then
returned to the grid floor.
 Ten such trials with an interval of 20 s are given.
 Evaluation
 A drug is considered to be effective, if the learned
helplessness is reduced and the number of failures to
escape is decreased.
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11. MURICIDE BEHAVIOUR IN RATS
 A selective inhibition of mouse-killing behavior in rats by
antidepressants.
 Method
 Male SD rats (300–350 g) are isolated for 6 weeks in
individual cages.
 One mouse is placed into the rat’s cage. About 10 to 30% of
rats kill the mouse by biting the animal through the cervical
cord.
 Only rats consistently killing mice within 5 min after
presentation are used for the test.
 Drugs are injected i.p. to the rats before the test.
 Mice are presented 30, 60 and 120 min after drug
administration. 11

12.  Evaluation
 Failure to kill a mouse within 5 min is considered inhibition
of muricidal behavior.
 The ED50 is calculated(dose which inhibits mouse killing
in 50% of the rats.)
 Modifications
 Injections of 5,7-dihydroxytryptamine into the lateral
hypothalamus increased mouse-killing behavior in rats
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13. POTENTIATION OF NOREPINEPHRINE TOXICITY
 Antidepressants block the re-uptake of biogenic amines into
nervous tissue. In this way, the toxic effects of
norepinephrine are potentiated.
 Method
 Male NMRI mice (22–25 g) are randomly assigned to test
groups of 10 subjects.
 The test drug, the standard or the vehicle are given orally 1
h prior to the s.c. injection of the sublethal dose of 3 mg/kg
noradrenaline.
 Evaluation
 The mortality rate is assessed 48 h post-dosing. ED50,or
dose which causes death of 50% of the treated subjects,is
calculated
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14. RESERPINE INDUCED HYPOTHERMIA
 Depletion of biogenic amines (noradrenaline, 5-
hydroxytryptamine, dopamine) in the brain induces not
only catalepsy and ptosis but also hypothermia in rodents.
 The decrease of body temperature induced by reserpine is
antagonized by antidepressants, MAO-inhibitors and
central stimulants.
 Method
 Groups of male NMRI mice (19–21 g body weight)are
used
 On the day before testing, they are dosed with 2 mg/kg
reserpine s.c.
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15.  Eighteen hours after reserpine administration, the animals
are placed into individual cages.
 The initial rectal temperature is determined by insertion of
an electronic thermometer
 Following administration of the test compound (either i.p.
or p.o.), the rectal temperature is measured again at 60
min intervals for 7 h.
 Evaluation
 Rectal temperature is recorded every hour.
 The difference in temperature from vehicle controls is
calculated for each time and the maximal difference is
scored.
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