Anxiety: PSY128 Lecture Support Material
Overview: This lecture shows you how the use of a behavioural paradigm (the Geller-Seifter paradigm) can be used to seek answers to two different but related questions:
  • What is the biological basis of anxiety?
  • Can we use a behavioural technique to screen for novel anti-anxiety drugs ( anxiolytics )?
Important points to look out for are:
  1. the acute versus chronic effects of benzodiazepines (BDP) in the paradigm
  2. the different effects of anxiolytic and antipsychotic drugs in the paradigm
The lecture is also a bit of a 'wolf in sheep's clothing' because I 'slip in' information on another neurotransmitter - serotonin. I will use this information to show you how one theory of the biochemical basis of anxiety can be tested.
Finally I will discuss some caveats that you need to be aware of: Drugs seldom affect behaviour by working on just one neurotransmitter system. Normally drugs affect several neurotransmitters at once, and they often have more than one mode of action. You need to appreciate this important point in case you are beginning to form the impression that a particular mental illness is the result of abnormal activity in one neurotransmitter system
Learning objectives
  • name 5 anxiety disorders defined in DSM-111-R
  • name 2 benzodiazepines
  • describe the Geller-Seifter paradigm
  • draw a diagram to show the effects of placebo and benzodiazepine treatments on responding in the Geller-Seifter paradigm
  • distinguish acute from chronic effects of anti-anxiety drugs on the Geller-Seifter paradigm
  • distinguish between the effects of major and minor tranquilizers on the Geller-Seifter paradigm
  • draw a diagram of the synthesis of 5-HT, include relevant enzymes
  • what drugs would you use to test the 5-HT theory of anxiety, and why?
  • evaluate the rationale for animal models of human behaviour

Anxiety disorders defined in DSM-111-R


SALAR: Study And Learning Assessment Resources

Measuring State Anxiety
Measuring Trait Anxiety

The purposes of these activities are to :

  • Present the items used in Spielberger's state and trait anxiety scales.
  • Show the relationship between scale scores and population percentile ranks
  • Show the relationship between individual questions and scale scores

Benzodiazepines

Types of benzodiazepines / anti-anxiety drugs / minor tranquilizers / anxiolytics Number of prescriptions written in USA

Effect of anxiolytic drugs in the Geller-Seifter paradigm

This paradigm, introduced by Geller and Seifter, involves a multiple schedule of reinforcement. In one segment of the schedule (signaled by a tone or light), responding is reinforced at irregular intervals (this is a V ariable I nterval or VI schedule),. In the second segment (signalled by a different signal) , every response is reinforced (this is a FR1 (F ixed R atio) or CRF (C ontinuous R ein f orcement) schedule); however these reinforced responses are also punished by the delivery of a brief, inescapable electric shock.. Consequently an animal trained under these contingencies of reinforcement, shows
Geller & Seifter found that anxiolytic drugs (drugs that reduce anxiety in humans)
Here is a diagrammatic representation of two cumulative records showing performance on the Geller-Seifter paradigm under placebo and drug treatments. Look here for an explanation of how a cumulative recorder works presented in an earlier lecture. performance on the Geller-Seifter paradigm under placebo and drug treatments

Effects of anti-anxiety drug on Geller-Seifter paradigm

The next figure shows the actual cumulative records from a rat treated with the antianxiety benzodiazepine drug Oxazepam .
The cumulative records are shown for the last control day and drug days as indicated. The slopes of these curves indicate response rates. The recording pen reset after every 3 minutes. The numbers indicate the number of of punished responses that occurred during 3-minute tone periods and the responses are indicated by short upward stokes of the pen. Downward strokes indicate rewarded responses that occurred during the unpunished periods. Note that the full 'anxiolytic' effect of the drug takes several days to emerge. For example, the rat makes fewer punished responses on days 1,2 and 3 than on days 12 and 22. Also the cumulative records show that unpunished responding tends to be depressed on the first few days of treatment and gradually recovers over the course of the experiment. This distinction between the acute and chronic effects of the drug will be explored in more detail in next year's lecture .

I have embedded a Java applet that allows you to magnify this image so that you can examine the animals behaviour in detail. The horizontal and vertical scroll bars enable you to move around the image.


This page is Java enhanced.
You will need a Java-capable browser to view its applet


Dose response effects of chlordiazepoxide on Geller-Seifter paradigm

This graph shows the effects of increasing doses of the benzodiazepine / minor tranquilizer drug chlordiazepoxide on punished and unpunished responding. Notice how at low and intermediate doses of the drug, the rate of punished responding increases whilst there is very little effect on unpunished responding. This suggests that the drug is having a specific effect on 'anxiety' rather than a general effect on response rate. However at very high doses both punished and unpunished behaviours are affected - there is a general decline in response rate - indicating a nonspecific / 'sedative' effect of the drug on the animals' behaviour
Dose response effects of chlordiazepoxide on Geller-Seifter paradigm

Dose response effects of chlorpromazine on Geller-Seifter paradigm

This graph shows the effects of increasing doses of the antipsychotic / major tranquiliser drug chlorpromazine on punished and unpunished responding. Notice that there is no evidence of a specific increase in punished responding at any dose of the drug. At higher doses there is a massive decline in both punished and unpunished bar pressing which reflects the 'sedative' effect of the drug.
Dose response effects of  chlorpromazine on Geller-Seifter paradigm

These results are examples of a body of evidence which shows that the pattern of responding (increase in punished responding with little change in unpunished response rate) in rats treated with benzodiazepines is specific to benzodiazepine drugs, and is not seen in animals treated with other classes of psychoactive compounds. This is a very important finding which suggests that the Geller-Seifter paradigm may be a good animal model for studying the biological bases of anxiety. The next step would be to try to understand whether anxiolytics work by affecting particular neurochemical systems.

Serotonin synthesis

It has been suggested that that serotonin (5-HT) mediates the effects of punishment on behaviour, and that benzodiazepines exert their anxiolytic effects via serotonin. I do not propose to go into details of this hypothesis this year, but this serotonin hypothesis provides a convenient 'hook' to begin our exploration of serotonin neurotransmision within the brain. The 5-HT hypothesis posits that antianxiety drugs reduce activity at serotonin receptor sites within the brain.
The diagram below shows the steps involved in 5-HT synthesis. Serotonin synthesis

Effects of drugs on 5-HT

You should be familiar with one strategy adopted by psychopharmacologists investigating a theory such as the 5-HT theory of anxiety: Briefly the effects of drugs that exert an influence over the 5-HT system are examined in an animal model of the human condition. The basic idea being that In fact early tests of this theory were promising. PCPA which blocks the enzyme tryptophan hydroxylase and thereby depletes the brain of 5-HT, has anti-punishment effects comparable to benzodiazepines.
The diagram below shows a number of drugs that effect 5-HT, can you predict how they would effect behaviour in the Geller-Seifter paradigm if the 5-HT hypothesis is a correct explanation for the biology of anxiety? Effects of drugs on 5-HT

Some comments and caveats


Despite the impression that you may have formed in these lectures, drugs seldom affect behaviour by working on just one neurotranmitter system. Normally drugs affect several neurotransmitters at once, and they often have more than one mode of action e.g. amphetamine affects catecholamine release and reuptake. Therefore it is generally accepted that the effects of psychoactive drugs involve several neurochemical processes. Furthermore neurotransmitter systems interact with each other, so that drug effects may 'cascade' through several systems. Nevertheless, drugs that are useful to psychopharmacologists tend to have relatively specific effects on one neurotransmitter system, and theories of the biological bases of mental illness tend to focus on specific neurotransmitter systems. This is certainly true of current work linking DA to schizophrenia. If you have read recent research on the biology of depression you may have gathered that the earlier CA theory of depression has lost favour and increasingly attention is focussed on the role of serotonin in depression. Often attention is narrowed down within a neurotransmitter system so that research focusses on particular receptor subtypes or particular neurotransmitter pathways within the brain.
At several points in these lectures we have presented animal models of mental illness. These animal models often serve several functions. For example they may be used as the basis of screening tests for new drugs, or as starting-off points on the road to understanding the biological basis of a particular human condition. The strengths and weaknesses of the various models should be clear to you but you should bear in mind that a model is only as good as the knowledge that went into its construction. There is a danger when animal models are used for drug screening that they may only reveal new medicines that work in a very similar way to the drugs used to construct the model in the first place. For example drugs that work as anxiolytics in the Geller-Seifter paradigm may do so simply because they have the same biochemical effects as benzodiazepines. This is all very well and good provided that the biological reason why benzodiazepines work in the animal model is the same as the way the drugs work to reduce human anxiety. If they differ, then a potentially important source of new and better drugs will be missed. Imagine a drug screening test that relied on the colour of the drug. Say- for the sake of argument - that all benzodiazepine molecules were blue. If a chemist synthesized a new molecule that was blue it would clearly be very dangerous to conclude that this new medicine would reduce anxiety in humans!
Point to ponder
Can you think of a better animal model of anxiety? Why would it be better than the model described in this lecture? How would you experimentally verify this claim?

Supplementary Reading

Here are URLs for some WWW pages covering Anxiety
  • The Internet Mental Health site has a wealth of information on anxiety as well as other psychiatric conditions.
  • The National Institute of Mental Health (NIMH) provide a very detailed discussion of anxiety, symptoms, treatment etc. . Here is a taster..
    Anxiety Disorders: Everybody knows what it's like to feel anxious-the butterflies in your stomach before a first date, the tension you feel when your boss is angry, the way your heart pounds if you're in danger. Anxiety rouses you to action. It gears you up to face a threatening situation. It makes you study harder for that exam, and keeps you on your toes when you're making a speech. In general, it helps you cope. But if you have an anxiety disorder, this normally helpful emotion can do just the opposite--it can keep you from coping and can disrupt your daily life. Anxiety disorders aren't just a case of "nerves." They are illnesses, often related to the biological makeup and life experiences of the individual, and they frequently run in families. There are several types of anxiety disorders, each with its own distinct features.
  • The Panic-Anxiety Page It is estimated that between 5% and 15% of the population will suffer from an anxiety-related disorder at some point in their lives. The good news is that anxiety disorders are among the most treatable of all psychological conditions.
  • 'When everyday worrying gets out of control ' by M. Patricia Solbach, PhD is a useful picture of what it feels like to be anxious. Here is a taster ....
    If your friends or relatives call you a "worrywart," it may be affecting more than your relationships. Worrying all the time can also affect your health. It doesn't matter if your worries are personal or global in scope.
    What was known by early physicians as "internal restlessness" is called "generalized anxiety disorder" (GAD) today. Possibly 3 percent of our population (roughly seven million people) suffers from such anxiety. It appears to be more common in women than men, with a ratio of 3.5 females to every male.
  • Treatment for Anxiety Disorders : Many people with anxiety disorders can be helped with treatment. Therapy for anxiety disorders often involves medication or specific forms of psychotherapy.
  • Pets can display anxiety:
    Separation anxiety is diagnosed in around 10% of the behavior cases referred to Canines of America by veterinarians in the New York City area. When left alone, most dogs find a familiar spot and go to sleep. However, a dog suffering from separation anxiety will become extremely anxious. Not understanding where you or your family has gone or if you will ever return, the dog exhibits behavior which may include chewing, barking, salivating, urinating, defecating, vomiting or escape behavior, such as chewing through walls, scratching through doors, busting out of cages or digging under fences if left outdoors. In some cases, the dog simply gets sick, perhaps due to some form of depression.

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Last updated Thursday, March 09, 2000 12:41:01
Copyright Dr. C.A.P. Kenyon 1994-00