The document discusses various types of anxiety disorders and preclinical models used to study anxiety. It describes definitions of anxiety and several anxiety disorders including generalized anxiety disorder, obsessive compulsive disorder, post-traumatic stress disorder, panic disorders, and phobias. Several commonly used preclinical anxiety models are explained including elevated plus maze test, open field test, light-dark test, staircase exploration, mirrored chamber test, and social interaction test. Evaluation parameters and procedures for each test are provided.
This file includes the general introduction to Alzheimer's, histopathology and Pharmacological treatment of Alzheimer's, preclinical screening models used in Alzheimer's. I hope this file may useful to life science students
Screening Methods for behavioural and muscle Coordinationpradnya Jagtap
Screening Methods for behavioural and muscle Coordination
A. Motor activity and behaviour
1. Method of intermittent observation
2.Open field test
3.Hole board test
4.Combined open field test
B.Test for muscle coordination
1.Inclined plane method
2.Chimny test
3.Grip strength
4.Rotarod method
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Screening Methods of Anti Anxiety AgentsAnupam dubey
Screening methods of anti anxiety agents
Guided By - Dr. Saumya Das,Associate Professor,NIET(Pharmacy Institute),Greater Noida
Presented By - Anupam Dubey,M.Pharm(Pharmacology)
NIET(Pharmacy Institute)
2020-2021
Preclinical screening of new substance for pharmacological activityShrutiGautam18
Preclinical study: A study to test a drug, a procedure, or another medical treatment in animals. The aim of a preclinical study is to collect data in support of the safety of the new treatment.
This file includes the general introduction to Alzheimer's, histopathology and Pharmacological treatment of Alzheimer's, preclinical screening models used in Alzheimer's. I hope this file may useful to life science students
Screening Methods for behavioural and muscle Coordinationpradnya Jagtap
Screening Methods for behavioural and muscle Coordination
A. Motor activity and behaviour
1. Method of intermittent observation
2.Open field test
3.Hole board test
4.Combined open field test
B.Test for muscle coordination
1.Inclined plane method
2.Chimny test
3.Grip strength
4.Rotarod method
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Screening Methods of Anti Anxiety AgentsAnupam dubey
Screening methods of anti anxiety agents
Guided By - Dr. Saumya Das,Associate Professor,NIET(Pharmacy Institute),Greater Noida
Presented By - Anupam Dubey,M.Pharm(Pharmacology)
NIET(Pharmacy Institute)
2020-2021
Preclinical screening of new substance for pharmacological activityShrutiGautam18
Preclinical study: A study to test a drug, a procedure, or another medical treatment in animals. The aim of a preclinical study is to collect data in support of the safety of the new treatment.
screening models for anxiolytics with detailed procedure and evaluation,
detailed classification about methods, pathophysiology of anxiety, components of anxiety, validity of anxiety,
difference bet pathological and physiological anxiety, different theories of anxiety, criteria of animal model, pharmacological manipulations, conditioned behavior, unconditioned behavior
Lecture from week 5 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
2. Anxiety Disorders
Definition : Anxiety is a condition of persistent
and uncontrollable nervousness, stress, and worry,
triggered by anticipation of future events,
memories of past events, or ruminations over day-
to-day events, with disproportionate fears of
catastrophic consequences.
It is characterized by feelings of apprehension,
insecurity, uncertainty or fear.
3. Generalized Anxiety Disorder(Excessive, unrealistic
worry that lasts six months or more)
Obsessive-Compulsive Disorder (Persistent, recurring
thoughts or obsessions that reflect exaggerated anxiety
or fears )
Post-Traumatic Stress Disorder ( Exposure to a
traumatic event)
Panic Disorders (Severe attacks of panic for no
apparent reason)
Phobias (Extreme anxiety about being judged by
others, or intense fear reaction to a specific object or
situation such as spiders, dogs, or Acrophobia).
Types of anxiety
4. Preclinical anxiety models
The goal of anxiety models is to produce a form of
abnormally elevated anxiety.
It should more closely resemble, by definition, the
pathological nature of human anxiety disorders.
Anxiety models are Models that generate lasting or
permanently heightened anxiety.
This can be achieved by acutely or chronically subjecting
animals to stressors before testing.
OR identifying genetic populations (inbred and selectively
bred strains) or engineering mutant mice with innate
anxiety-like phenotypes.
5. This approach has proven to be valuable for screening novel
anxiolytics and testing the pharmacoselectivity of putative anxiolytics .
Emerging genetic technology is the optogenetics. It will be integral to
future basic anxiety research.
optogenetics is the combination of genetic and optical methods to
control specific events in targeted cells of living tissue in the
millisecond timescale.
Optogenetic approaches have been used to map neural circuits in the
amygdala that contribute to fear conditioning.
6. PRECLINICAL EVALUATION OF
ANXIOLYTICS
In-vitro Methods:
1. GABA receptor binding
2. Benzodiazepine receptor: [3H]-flunitrazepam binding
assay
3. Serotonin (5-HT1A) receptor: binding of [3H]-8-hydroxy-
2-(di-n-propylamino)-tetralin ([3H]-DPAT)
4. Serotonin (5-HT1B) receptors in brain: binding of [3H]5-
hydroxytryptamine ([3H]5-HT)
7. The following parameters are calculated:
• Total binding
• Non-specific binding
•Specific binding= total binding– non-specific
binding.
8. In Vivo Methods
Methods based on unconditioned
(spontaneous) response:
Exploratory activity
Elevated plus-maze (other
Mazes such as Y, X,T, Radial, water
and Zero Maze)
Open field/Closed field
Light-dark model (two
compartment box)
Staircase exploration
Hole board test
Mirror chamber test
Social behavior
Social interaction
Isolation induced aggression
Anticipatory anxiety in mice
Predator
Defense test battery in rats
Human threat (Primates)
Odor associated avoidance
behavior
Others
Novelty suppressed feeding
Schedule induced polydipsia in
rats
Marble burying
Cork gnawing
Stress induced hyperthermia
9. • Methods based on conditioned (learned) response:
Punishment models:
• Four plate test
• Punishment induced operant behavior
• Conditioned emotional response
Conflict models:
• Vogel punished drinking
• Geller seifter conflict (marmoset, pigeon conflict)
• Shock probe conflict procedure
Respondent conditioned with aversion stimuli:
• Conditioned suppression
• Potentiated startle response
• Electric brain stimulation
Frustration (non-reward) test:
• Shock probe- burying test
10. In Vivo Methods
Validity
• Face validity : A feature that is assessed (for a test or model of anxiety) by
determining how closely the model or test resembles human anxiety
symptoms.
• Predictive validity : whether the model or test reliably responds to clinically
efficacious anti- anxiety medications.
• Construct validity : whether the degree to which the model or test recruits
the same underlying neurobiology as implicated in human anxiety.
11. Elevated Plus Maze Test
For selective identification
of anxiolytics and anxiogenic
drugs
Anxiolytics –decrease
anxiety – increase open arm
exploration time.
Anxiogenics – decrease open
arm exploration time.
Most widely used method;
male mice/rats used.
12. Experimental Design
• Group I : control
• Group II : standard
• Group III : test treated with dose x
• Group IV : test treated with dose 2x ….
13. The rats weighing around 200g - housed in pairs
for 10 days prior to testing; 6animals selected for
each group.
Test drug administered 30min prior to
experimentation by i.p route.
The rat is then placed in the centre of the
maze facing one of the enclosed arms.
Animals were allowed to explore in the maze for 5
min. Observations will done from adjacent room via
remote TV camera.
14. Parameters Measured During Next 5 minutes:
o time spent in the open arms
o entries into the open arms
o time spent in the closed arms
o entries into the closed arms
o total arm entries
15. Evaluation of results:
o Motor activity and open arm exploratory activity determined.
o Values of treated groups expressed as % of control values.
o Benzodiazepines and valproate – decrease motor activity
increase exploratory time.
Anxiolytic effect indicated by:
o Increase in the proportion of time spent in open arms.
o Increase in the proportion of entries into open arms.
16. Open-field Test
This test, originally designed by
Hall on rats.
It consists of placing an animal
in an unknown environment
with surrounding walls, so as to
observe a number of behavior
patterns, including:
The tendency to stay on the
periphery of the field without
entering the centre (called
thigmotaxis and often
interpreted as anxious behavior)
level of defecation and
urination.
17. Anxiolytic agents should lead to increase in this ratio.
The open field floor is divided into squares
Animals are tested individually, always being placed in
the same position.
Duration of test is usually 5 min.
Higher levels of anxiety should mainly lead to decreases
in the ratio ‘number of squares
visited in centre/number of squares visited on periphery.
18. Light – dark model
• Crawley and Goodwin
(1980).
• Mice and rats tend
to explore novel
environment ,but
retreat from
brightly- lit
open field.
19. In a two chambered system, where animal can freely move between brightly
lit open field and dark corner, they show more crossings between two
chambers and more locomotor activity after treatment with anxiolytics.
Methodology
• Test apparatus- light and dark chamber divided by photocell equipped zone.
• Polypropylene animal cage 44x21x21 cm, darkened with black spray over on-
third of surface.
• Partition containing 13cm long x 5cm high opening separates the dark one
third from bright two thirds of the cage
• Cage rests on an animex activity monitor, which counts the locomotor
activity.
• Four sets of photocells across the partition, automatically counts movement
through the partition and clocks time spent in light and dark
20. Male mice with a weight between 18 and 24 g are used
Test drug administered 30min prior to experimentation by
i.p. route.
The animal is placed in the cage and observed for
10 min.
21. Observation
o No. Of crossings through the partition between the light
and dark chambers compared with total activity counts
during the 10 min.
o Loco motor activity also monitored.
Evaluation:
o Anxiolytics like diazepam & buspirone increase locomotor
activity and no. Of crossings.
o Non anxiolytics - not effective in this model.
23. • When introduced into a novel environment, rodents
experience a conflict between anxiety and exploratory
behavior manifested by increased vigilance and behavioral
activity
• Staircase climibing reflects exploratory or locomotor
activity
• Rearing behavior is an index of anxiety state
• The no. of rearing and steps climbed to be recorded for
period of 5 minutes
• Decrease in rearing behavior and increase in steps climbed
is characterization of anxiolytic effect
24. Male mice (Charles River strain) with a weight
between 18 and 24 g are used
Test drug administered 30min prior to
experimentation by s.c. route.
The animal is placed on the floor of the box with
its back to the staircase.(staircase is composed of
five identical
steps 2.5 cm high, 10 cm wide )
25. Mirrored chamber test
Novel stimulation evokes both exploration and anxiety and therefore generates
approach avoidance conflict behaviour
• It is hypothesised that distortion of readily traversed environment by a chamber of
mirror might produce aversion to entry
• Mice are exposed to the chamber of mirror
• Extended latency to enter the chamber of mirror used as a parameter for anxiety
analogy
• Anxiolytics reduce this latency in dose dependent manner.
26.
27. Social interaction in rats
• Purpose and rationale : In an
unfamiliar and brightly lit
environment, the normal social
interaction of rats ( sniffing,
nipping, grooming) is suppressed.
• Anxiolytics counteract this
suppression.
28. Animals placed in groups of 5 each in a perspex open
topped box
1hr before test,2 rats from separate housing treated
with test compound orally
Placed in box with 60W bulb and behavior observed
for 10minutes
social interactions like sniffing, rearing, crawling over
the partner are observed
29. Procedure:
• Male sprague-dawley rats (225-275g) are housed in groups of 5 animals
• Apparatus: perspex open-topped box (51x51x 20cm) with 17x17cm marked areas on the
floor.
• One hour prior to the test, 2 naïve rats from separate housing cages are treated with
test compound orally
• They are placed into the box (with 60W bright illumination 17cm above) and their
behaviour is observed over a 10 min period.
• 2 types of behaviour can be noted:
• Social interaction between the animals is determined by timing the sniffing of
partner, crawling under or climbing over partner and following partner.
30. • Exploratory motion is measured as the number of crossings of the lines marked on
the floor of the test box.
• Six pairs are used for each dose
• Evaluation: values of treated partners are compared with the data from 6 pairs of
untreated animals using single factor analysis of variance followed by Dunnett’s
test
31. Isolation induced aggression
o Male mice subjected to isolation
Develop aggressive behavior towards
other animals of same sex.
32. Male Mice kept isolated for 6weeks & aggressive behavior
tested.
Male mice accustomed to live together placed in cage of
isolated mice for 5minutes
Isolated mice attacks intruder aggressiveness observed
Drugs given to isolated mice s.c or orally; aggressive behavior
tested at 60, 120,240 minutes (oral route)
If drug active- decrease in aggressiveness Attenuation of
fighting reaction
33. Human threat (primates):
Suarez and Gallup (1982) first demonstrated human
being as a predator. It can be studied in various ways of
avoidance of experimenter. One method involves an
experimenter sitting in a chair in the center of a floor
containing chicks. The proximity of the chicks to the human
is then determined usually by numbering imaginary zones
around the occupied chair. The chicks are then given an
‘avoidance score’ of 1-5 (either in ascending or descending
proximity to the experimenter) based on a total of their
positions over a certain time frame. Another method is
called the ‘box plus experimenter’ method. This test uses
the same premise as the above method; however, during
the box plus experimenter test, the human is seated behind
a wire mesh wall at the end of an arena. The chick is
scored on its approach or avoidance to the experimenter
behaviors. Again, higher avoidance suggests higher fear
levels.
34. Odour associated avoidance behaviour:
The predatory odour avoidance model relies upon
the apparently innate fear that rodents have for the odor
of their natural predators, such as cats and foxes. Rats
tend to avoid such odors and engage in a variety of
defensive behaviours in their presence. Novel methodology for testing is given by
Dielenberg and McGregor (1999). Testing chambers comprised of a rectangular arena
with perspex walls (60 cm x 26 cm x 36 cm) and a metal grid
floor which was raised 2 cm above a tray containing wood shavings. At one end of the
chamber was a small wooden box (21 cm x 24 cm x 22 cm) termed the ‘hide box’. On
the front wall of the hide box was a small square hole (6 cm x 6 cm) that allowed rats to
enter the box. On the opposite wall of the apparatus to the hide box was an
alligator clip positioned 4 cm above the metal grid floor. During testing, a piece of cat
collar was attached to the clip as shown in Fig.8. A domestic cat wore this cat
collar for a period of three weeks before the start of the experiment. Photocell
detectors were placed at opposite ends of the chamber. The placement of the
photocells allowed determination of: i) the amount of time the rats
spent in close vicinity to the cat collar (approach time); and ii) the amount of time
spent in the hide box (hide time). During testing, the room in which the chambers
were situated was illuminated by a 40 W red-light suspended
1.5 m above the apparatus.
35.
36. Vogel punished drinking
This test is a well-known method used in rats,
designed by Vogel et al.
• Recently, this test has been reported to successfully
detect anxiolytic-like action of diazepam .
• In this test, thirsty animals gain water reward
through a water spout, but at the expense of receiving a
mild electric shock delivered to the tongue.
Rats are deprived of water for 48 hrs
• Then placed in chamber with watersource
• sprague dawley rats are used in this model
37. Electric circuit is connected between
drinking tube and floor of cage.
i.p injection of drugs are given; 30min later
rats placed in cage and allowed to drink
water and shock given after 20 licks
For 3minutes next shocks are given for
every 12th lick
No. of shocks delivered in 3min noted for
each animal, no. of shocks received after
treatment noted
a water bottle with metal drinking tube is
fitted to the animal housing
38. o number of accepted punishments (electric
shock) are measured during conflict period
Anxiolytic effect :
o increase in the accepted shocks.
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.
39. Geller seifter conflict (marmoset,
pigeon conflict)
.
•Conflict is produced by availability of
reinforcement with punishment
• Experimentally induced conflict by punishing
food rewarded behavior has been used to
differentiate between various psychoactive
drugs by Geller and Seifter
• Male albino rats with a body weight of 300–400
g are housed individually.
• They are food deprived until the body weight is
gradually reduced by approximately 20% of
original and it is maintained at this level by
restricted food diet.
• Conditioning is carried out with a flash of light, a
single lever, a liquid dripper, and a grid-floor
connected to a shocker
• The animals are trained to lever press for the milk
reward in two distinct response-reward sections.
40. • Anxiety or “conflict” segment (3 min)
• a dipper of milk is delivered in response to each
lever press (continuos reinforcement schedule
=CRF),
• accompanied by aversive foot-shock through the
grid floor
• Creates a conflict between milk reward and the a
painful foot shock
“nonconflict” segment (15 min)
• lever presses produce a drop of milk only at variable intervals of time from
60 to 210 s with an average reward of once per 2min
• No shocks are administered
• Four cycles of 15 min nonshock variable interval segments followed by a
three minute CRF-conflict period phase
• The total number of lever presses during the conflict periods (CRF) and the
non-conflict periods (VI) are counted.
• Anxiolytic effect :An increase of lever presses
in the conflict periods
41. Electric brain stimulation
• Electrical stimulation of brain aversive areas, in
particular the midbrain central gray, induces defensive
reaction and/or flight behavior in several species
• Used as an animal model of anxiety or of panic
attack.
• Most studies used intracerebral microinjections of
neurotransmitters, their agonists and antagonists to
elucidate the mechanisms of aversive or antiaversive
effects
42. Foot shock induced aggression
• GABA is involved in control and agrgressive
behaviour of animals.
• Benzodiazepines are thought to produce
anxiolytic effects by binding to a specific high
affinity site on GABA-A receptor
• So aggressive and fighting behavior has been
extended for GABAergic anxiolytic drug
screening.
43. The fighting behaviour consists of vocalization, leaping,
running, rearing and facing each other with some attempt to
attack by hitting, biting or boxing
Two mice are placed in a box with a grid floor consisting of
steel rods
A constant current of 0.6 or 0.8mA is supplied to the grid floor
is delivered for 5 s followed by 5 s. intermission for 3 min.
The total number of fights are recorded for each pair during
the 3-min period.
44. Pathological anxiety
(Neurochemically - induced anxiety)
mCPP - [ 1-(3-chlorphenyl) piperazine] a 5HT 1c
agonist.
o mCPP induces hypophagia and
hypo-locomotion , inhibits social interaction,
diminishes exploratory activity in light-dark
box test, hyper therimia etc,.
o Antagonism of these symptoms is used for
screening of anxiolytic drugs.
45.
46. Anticipatory anxiety in mice
Anticipatory anxiety in mice
• When 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
47. 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- 1.3˚C
48. 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.
49. 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.
50. Parameters measured :
o time spent in both sides (horizontal,
vertical activity)
o frequency of motion
o number of transition
Anxiolytic effect :
o increase in parameters measured in
the light/dark box or in number of
transitions if test is active.
51. A method is described for reproducible measurement of ultrasonic
vocalization induced by tail-holding stress in rat pups. The anxiolytic
benzodiazepines, chlordiazepoxide, diazepam, and CL 218872, reduced
the ultrasounds at doses inducing little CNS depressant activity. Gross
behavioral disruption such as sedation (muscimol, prazosin, and
chlorpromazine), tremors (yohimbine), myoclonus (MK212), and
immobility (morphine) resulted in reduction of ultrasounds. Non-
behaviourally active doses of these compound or any doses tested of
mephenesin, amphetamine, amitriptyline, haloperidol, and naloxone did
not affect the ultrasounds. Metergoline inhibited ultrasounds at doses
producing little change in overt behavior. This method is proposed as a
convenient model of anxiety which may also be influenced by central 5-
hydroxytryptamine transmission.