In vivo model of depression


Published on

1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

In vivo model of depression

  1. 1. IN VIVO MODEL OF DEPRESSION Umangi Chauhan NIPERA1214PC05 1
  2. 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. 2
  3. 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. 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. 4
  5. 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 5
  6. 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. 6
  7. 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. 7
  8. 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. 8
  9. 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. 9
  10. 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. 10
  11. 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. 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 12
  13. 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 13
  14. 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. 14
  15. 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. 15