screening of antianxiety drugs

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  • In vivo methodsMethods based on unconditioned (spontaneous) response:Exploratory activityElevated plus-mazeWater maze test Light-dark model (two compartment box)Staircase explorationSocial behaviourSocial interactionIsolation induced aggressionAnticipatory anxiety in mice *

  • Methods based on conditioned (learned) response:Conflict modelsVogel punished drinking/ Vogels lick conflict modelChemical induced methodmCPP induced anxiety in rats

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  • 2 open arms and 2 closed arms of 50 x 10 x 40cm dimensions

    Open roof arrangement

    Two open arms are opposite to each other.

    Maze elevated at 50cm height above the ground.*

  • Experimental Design Group I : controlGroup II : standard Group III : test treated with dose x Group IV : test treated with dose 2x .

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  • *Animals were allowed to explore in the maze for 5 min. Observations will done from adjacent room via remote TV camera.

  • Parameters Measured During Next 5 minutes:

    time spent in the open arms

    entries into the open arms

    time spent in the closed arms

    entries into the closed arms

    total arm entries

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  • Evaluation of results:Motor activity and open arm exploratory activity determined.Values of treated groups expressed as % of control values.Benzodiazepines and valproate decrease motor activity and increase exploratory time.

    Anxiolytic effect indicated by:Increase in the proportion of time spent in open arms Increase in the proportion of entries into open arms

  • Circular tank of 100-150 cm diameter with 20-30 cm wall

    A platform of 9-10 cm hidden 2-3 cm below water level

    Add titanium dioxide susp. to make water opaque.

    Temp : 23C.*

  • Rodents have exploratory activity

    Animals placed in 2 chambered systems, where they can freely move between a brightly lit open field and a dark corner.

    After treatment with anxiolytic - show more crossings between the two chambers and more locomotor activity.

    Number of crossings between the light and dark sites is recorded.*

  • Methodology Apparatus - a dark and a light chamber divided by a photocell equipped zone.

    Polypropylene animal cage (44 x 21 x 21 cm) is darkened with black spray over 1/3rd of its surface.

    A partition containing 13cm(l) ,5 cm (h) opening is used for separating the dark one-third of the cage.

    This case rests on an activity monitor which counts total locomotor activity.

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  • An electronic system consisting of 4 sets of photocells across the partition. It automatically counts movements through the partition and records the time spent in the light and dark compartments.

    Animals- treated 30 min before the test with drugs or vehicle given i.p. placed in the cage and observed for 10 min.

    Groups of 6-8 animals used for each dose.

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  • Observation No. Of crossings through the partition between the light and dark chambers compared with total activity counts during the 10 min.Loco motor activity also monitored.Evaluation:Anxiolytics like diazepam & buspirone increase locomotor activity and no. Of crossings.Non anxiolytics - not effective in this model.

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  • Animal used: Male NMRI strain mice

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  • Evaluation of results:

    No. of animals with complete suppression of aggressiveness.

    Reaction time noted.

    Graduated scale of inhibition of aggressiveness is established.

    Results of test group animals is compared with the control group results.*

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  • *Methodology

  • Parameters measured : exploration, sniffing, rearing, social contacts, sexual behaviour, attack, fighting, biting ,defensive posture, immobility and climbing over the partner.

    Evaluation :Values of treated partners compared with data from control animals ANOVA and t - test used.

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  • mCPP - [ 1-(3-chlorphenyl) piperazine] a 5HT 1c agonist.

    mCPP induces hypophagia and hypo-locomotion , inhibits social interaction, diminishes exploratory activity in light-dark box test, hyper therimia etc,.

    Antagonism of these symptoms is used for screening of anxiolytic drugs.*

  • Anticipatory anxiety in miceWhen group housed mice are removed one by one from their former cage, the last mice always have a higher body temperature than the 1st one.The anticipatory increase in temperature was prevented by prior administration of diazepam & buspirone

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  • *Test drug/solvent administered p.o to all the 18 animals. Record the basal temp by removing 1st 3 animals/group after 30 min Difference in the mean value of last three animals and basal value is calculated Vehicle treated group 1- 1.3C

  • *Male Sprague Dawley rats (200- 250g) are housed in groups of 6; exposed to 12 hour light/dark cycle with free access to food and water.

  • mCPP Induced Anxiety -Locomotion Study Test compound or vehicle are administered orally 1h or i.p 30 min before the locomotion test.

    mCPP is injected i.p. in a dose of 7 mg/kg 20 min before the test.

    The animals are placed individually in an automated locomotor activity cages and locomotion is recorded for 10 min.

    Anxiolytic effect : disinhibition of locomotion.

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  • Parameters measured : time spent in both sides (horizontal, vertical activity) frequency of motion number of transition

    Anxiolytic effect : increase in parameters measured in the light/dark box or in number of transitions if test is active.*

  • Source of anxiety: thirsty, native rats are administered shocks while licking water.

    Animals used: Sprague dawley rats.*

  • Apparatus*Clear Plexiglas box (38 x 38 cm) has a steel grid floor.A water bottle with metal drinking tube at 3 cm above the grid.A circuit is connected b/w the drinking tube and steel floor, so that the circuit completes if animal licks the tube.

  • Methodology *

  • Parameters measured:number of accepted punishments (electric shock)

    Anxiolytic effect :statistically significant increase in the accepted shocks.*

  • Staircase apparatus*

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