SCREENING PROCEDURES FOR AMNESIA

PRESENTED BY JATHIN SM.Pharm , First Semester.

GUIDED BY Mrs. D.D.BANDAWANEM.PHARM, PhD, H.O.D, PHARMACOLOGY

PES MODERN COLLEGE OF PHARMACYNigdi, pune.

CONTENTS

Introduction

Objective

Screening procedures

Conclusion

Reference

INTRODUCTION

Memory Memory means the conservation of certain conditions,

their reproduction and their localisation in the past. The three elements are of unequal values; The first two are necessary , indispensible ; The third , what in the language of the school is called “Recollection” , completes the act of memory but does not constitute it.

Amnesia In neuropsychology amnesia is most commonly used to

describe a patient suffering from what is called as Amnesic syndrome , which can be defined as permanent global disorder of memory following brain damage.

OBJECTIVE

Amnesia is a topic that is of high importance in Indian scenario as the number of cases on it are increasing and the awareness of this disease is very low.

My aim is to study the screening procedures for amnesia and giving a brief account of drug therapy on it.

CLASSIFICATION

Amnesic syndrome It is an organic brain syndrome, caused by

head injury Includes: Korsakov's syndrome or psychosis Dissociative amnesia Results from a psychological cause. Anterograde amnesia loss of short-term memory, the loss or impairment of

the ability to form new memories through memorization.

Retrograde amnesia loss of pre-existing memories to conscious

recollection, beyond an ordinary degree of forgetfulness.

PATHOPHYSIOLOGY

The most well-described regions indicated in this disorder are the medial temporal lobe (MTL), basal forebrain, and fornix.

Hypertensive surge is hypothesised as one of the cause for amnesia .

excessive glucocorticoid stimulation has been shown to induce loss of dentritic spines & synapse, Shrink the hippocampus and impair cognition in both animal models and humans.

MANAGMENT OF AMNESIA

The primary goal in the management of amnesia is to treat the underlying cause.

A regimen of anticancer drugs (chemotherapy) along with radiation treatments (radiation therapy) may be indicated for individuals with cancerous brain tumors.

SCREENING PROCEDURES

Behavioral models for studying drugs or conditions that affect cognitive processes rely on a stimuli to induce an aversive state within the organism.

Once an animal has learned to escape from aversive events, the next favourable strategy is to try to avoid those aversive events totally.

METHODS OF SCREENING

Discrimination learning 1. Morris water maze2. Radial arm maze3. Y-Maze4. Figure 8 maze5. Modular mazes6. Stone T-maze Avoidance behaviour

7. Three-panel runway apparatus8. Elevated Plus-maze9. Two-way shuttle box

DISCRIMINATION LEARNING1.MORRIS WATER MAZE A task was developed where rats learn to

swim in a water tank to find an escape platform hidden under the water (Morris 1984).

As there are no proximal cues to mark the position of the platform, the ability to locate it efficiently will depend on the use of a configuration of the cues outside the tank.

Learning is reflected on the shorter latencies to escape and the decrease on the length of the path to find the platform.

MORRIS WATER MAZE

2.RADIAL ARM MAZE

The rat uses spatial information provided by the distal cues in the room to efficiently locate the baited arms.

The radial arm-maze allows the study of spatial reference and working memory processes in the rat.

working memory procedures have a major temporal component as the information resented in the maze (arms baited) is useful for one session but not for subsequent ones.

Correct choices in the radial arm-maze are rewarded by food.

3.Y-MAZE

A variety of Y-maze task paradigms are available for the evaluation of spatial working and long-term memory in rodents.

Using food or sweetened water as an incentive to reach the goal, animals are either required to execute a specific search sequence or minimize time/errors in the quest for a reward.

The spontaneous alteration task paradigm is the simplest version of Y-maze task used to measure the spatial working memory in rats.

4.FIGURE 8 MAZE

Figure 8 maze, used to measure spatial ability of animals, is a unique task paradigm designed basically to provide a classic common ‘choice point’ (Figure 4) with gated entry and exit points.

It may also be equipped with photo-cell detection system for automatic recording of the animal behaviour.

However, this task is not being used currently, except for supportive information.

5.MODULAR MAZES

These mazes are built on the concept of construction complex mazes with simple maze segments. Using the six basic segments (Figure 8) a number of complex mazes can be constructed by adjoining and increasing numbers and variations in the basic segments.

Each basic segment comprises a specific maze pathway constructed on a one square foot platform or in any other required dimension. Platforms may be mechanically joined to complete the maze.

Further, the junction of platforms may be demarcated with photocell sensors that defined specific maze sections for automated monitoring studies using commercially available photo-cell monitors or video tracking systems.

6.STONE T-MAZE It is complex modular maze used to assess

the mixed spatial workin, cue and taxon learning skills in rats.

The maze has only one correct route. A delicious food was placed in the goal box at the end of the maze.

A trial started when the rat had moved both forelimbs, snout, and upper body out of the start box. The trial ended when the rat reached the goal box and made contact with the food reward or after 5 min had elapsed.

AVOIDANCE BEHAVIOUR7.THREE-PANEL RUNWAY APPARATUS A straightforward avoidance situation

features a fixed aversive gradient which can be traversed by the animal.

The shock can be avoided when the safe area is reached within the time allocated.

The time the animal needs to reach the safe area on both days is measured. In addition, the number of errors (not reaching the safe area) is recorded.

8.ELEVATED PLUS-MAZE

elevated plus-maze has been recently extended to measure the spatial long-term memory in animals.

It is based on the apparent natural aversion of rodents to open and high spaces .Animals spend more time in the enclosed arms because they dislike the open arms.

transfer latency (the time in which the animal moves from the open arms to the enclosed arms) was markedly shortened if the animal has previously experienced entering the open arms.

ELEVATED PLUS-MAZE

9.TWO-WAY SHUTTLE BOX

Compared to runway avoidance, shuttle box avoidance (two-way-shuttle-box) is a more difficult task.

Since the animal is not handled between trials, the shuttleboxcan be easily automated.

The time the animal needs to reach the safe area on both days is measured.

In addition, the number of errors (not reaching the safe area) are recorded.

INDUCTION OF AMNESIA IN LABORATORY ANIMALS

Drug-induced state dependent learning Animals trained on a task under some drugs

often show a failure of learning performance when they are tested in the absence of the drugs. The failure, however, is ameliorated when the drugs are reintroduced.

Electroshock-induced amnesia Amnesia can also be induced in experimental

animals by electroshock (ES) stimulation. Presentation of electroshock by silvercorneal electrodes induces clonic-tonic seizures and impair memory.

BRAIN LESION-INDUCED COGNITIVE DYSFUNCTION

Lesions have been produced with several different neurotoxic and electrolytic techniques and several cholinergic agents have been utilized to reverse the resulting deficits.

A selective cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A) has been widely used for the experimental induction of cognitive deficits.

Novel drug ApproachDrug in question

Aim Materials & methods

Biostatical method

Result Conclusion

stevioside The present study was

undertaken to explore the potential of stevioside in

memorydysfunction

of rats.

Morris water maze (MWM)

test was employed to

assess learning and

memory. Memory

impairment was produced by scopolamine (0.5 mg/kg,

i.p.) in animals.

The results are expressed as

mean ± standard error of

means (S.E.M.). The data of

behavioral results were statisticallyanalyzed by one-way analysis of

variance (ANOVA)

followed bypost hoc Tukey’s multiple range

test using Sigma Stat Statistical

software version 3.5.

Pretreatment of stevioside (250

mg/kgdose orally) significantly

reversed scopolamine-

induced learning and

memory deficits along

with attenuation of scopolamine-induced rise in

brain AChE activity and

brain oxidativestress levels.

It may be concluded that

stevioside exerts a memory-

preservative effect in

cognitive deficits of rats possibly

through its multiple actions.

Drug in question

Aim Materials & methods

Biostatical method

Result Conclusion

ß-alanine (a glycine

agonist),

study was undertaken

to investigate

the effects of ß-alanine (a

glycine agonist), on learning and memory in

mice.

The learning and memory

parameters were assessed, using elevated plus-

maze and passive-

avoidance apparatus.

All results were expressed as

mean ± standard error

of mean (SEM). All the groups were analyzed using Kruskal -Wallis ANOVA. For comparison of two groups, Mann-Whitney

U-test was applied.

ß-alanine at both the doses (10 and

20 mg/kg), significantly

improved learning and memory of

young- and aged- mice. ß-alanine also reversed

scopolamine (0.4 mg/kg i.p.),

ethanol (1.0 g/kg i.p.) and

diazepam (1.0 mg/kg i.p.) -

induced amnesia in young mice.

The probable underlying

mechanism of the memory-

enhancing effect of ß-alanine appears to be related to its

antioxidant, anti-amyloid and

procholinergic activities.

Drug in question

Aim Materials & methods

Biostatical method

Result Conclusion

Brahmi Identify the ingredients

(of the complex

formulation), which

purveyed the cognitive

benefits, we studied, Brahmi

Adult, male, rats were

randomized to receive Brahmi,

piracetam, or vehicle from days 1 to 15.

Rats were trained in a T-maze using a food-driven paradigm.

A three-way, mixed-model,

repeated-measures

analysis of variance was

used.

All showed varying but generally

favourable profiles in

the attenuation

of ECS-induced

retrograde and

anterograde amnesia.

Brahmi do not in themselves improve learning; however,

attenuates the amnestic effects of

ECS.

Herbal Drugs

Drug in question

Aim Materials & methods

Biostatical method

Result Conclusion

Ocimum tenuiflorum

To assess the potential of Ocimum tenuiflorum Linn. as a nootropic

Passive avoidance paradigm served as the exteroceptive

behavioural model.

one-way ANOVA,

followed by unpaired ‘t’

test.

O. tenuiflorum extract increased

step-down latency and acetyl

cholinesterase inhibition

significantly.

O. tenuiflorum can be employed

in the treatment of cognitive

disorders such as dementia and

amnesia.

Argyreia speciosa

The present work was

undertaken to justify the traditional

claim of the plant as

nootropic and antiamnesic

agentin mice.

Exteroceptive behavioural models

suchas elevated plus maze and Water

maze were used to assess the short-term

memory, whereas, scopolamine and natural ageing-

inducedamnesia served as

interoceptive models

The data were expressed as mean6SEM.

The datawere analysed using one-way

ANOVA followed by

Tukey— kramer tests.

Pre-treatment with EAAS (100 and 200

mg/kg, p.o.)

significantly attenuated

scopolamine and ageing-induced

amnesia.[ The ethyl acetate and ethanolic fractions (EAAS) of roots were selected

for the study]

The results indicate that A. speciosa has

significant nootropic and antiamnesic

activity,Justifying its

traditional use in Ayurveda.

CONCLUSION

Although a wide variety of behavioural models for the evaluation of learning and memory processes are currently being used, the interpretation of behavioural parameters in many of these tasks is still ambiguous.

Drug effects should be tested in different types of tasks that tap different aspects of behaviour to exclude alternative explanations for the performance in a cognitive task.

Rapid developments in the field of neurobiology of learning and memory processes may hopefully lead to an improved understanding of the pathophysiology of several disorders that are associated with cognitive dysfunction.

REFERENCE

1. Theodule armand ribot, Diseases of memory , an essay in the positive psychology. page no. 10-25

2. H. Gerhard vogel , drug discovery and evaluation pharmacological assays second edition page no. 624-634

3. WHO bluebook -The icd-10 classification of mental and behavioural disorders.

4. Assessment of nootropic and amnestic activity of centrally acting agents by d.S. Reddy[department of pharmacology, university institute of pharmaceutical sciences, punjab university.Chandigarh.]

5. Antiamnesic effect of stevioside in scopolamine-treated rats deepika sharma1, munish puri, ashok k. Tiwary, nirmal singh, amteshwar singh jaggi ijp

6. anti-amnestic properties of brahmi and mandookaparni in a rat model chittaranjan andrade, j. Suresh chandra indian journal of psychiatry

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