CHEMISTRY OF BEHAVIOR

[Music] this woman is mentally ill she is being treated with psychoactive drugs that will affect her behavior what is god saying to you now sally this is me when i came to the hospital i was very upset from many worries they make me sick i could not even talk to the doctor this is me four days later after the doctor gave me some medicine to help me now i'm not so mixed up i talked to him okay this is me when i'm ready to leave the hospital i am better now [Music] so [Music] i'm john darling one out of every 10 americans requires treatment for mental illness and drugs as you have just seen can show dramatic results for they produce profound effects on human behavior during the last 10 years they have revolutionized the care of the mentally ill but just how do these psychoactive drugs work this is the key question in the field of psychopharmacology many scientists are searching for the full answer the major contribution of the psychologist in this search is his specialized ability to observe and to measure behavior engaged in research of this kind is the chairman of the psychology department at the university of indiana dr roger russell the first thing we can say about psychoactive drugs is that they affect behavior now this may seem very obvious to you but it is of tremendous importance not only that drugs affect behavior but that specific drugs affect behavior in specific ways the psychologist has developed methods and techniques for observing and measuring behavior these procedures have double value first they may be used to obtain knowledge which is essential to the general medical use of drugs including undesirable side effects and second they may be used for research at the basic level all aspects of behavior from complex problem solving to general level of activity are important to us we do a great deal of our testing with animals the research designs are complex and they take some time and care to interpret the results let me give you some simple demonstrations of the sort of thing we do now this is a test of complex problem solving this rat has learned that there's food at the other side of this closed field the barriers in the field may be rearranged to form different problems the rat has not seen this particular problem before so if we put him in the starting box and release him we'll be able to measure the time it takes for him to go from the start box to the food well that animal took 14 seconds to run the maze that's a very good time for the first trial on any animal i'm going to take him out put him in this cage while we see how well this second animal can do this is a comparable animal in terms of his past performance this animal has been drugged it's also the first time he's seen this particular problem let's see how he compares with the animal you've just seen i'll treat him in exactly the same way now you see it took him 32 seconds to solve the problem for this first trial and you also may have noticed that his coordination was definitely not as good as his partners now this is a kind of complex behavior made up of many simple components we're as interested in the simple components as we are in the complex behavior itself this equipment is designed to study what we call a simple escape response when i put this normal rat in the water he swims as rapidly as he can to the escape platform at the other end and here is how a drugged rat again with the same drug responds to the same situation many different species of animals are used in studying the effects of drugs upon behavior in terms of the practical uses of drugs monkeys have advantages as experimental subjects in being more similar to man than rats for example but no animals reactions are identical with man's therefore it is always essential that research be conducted with human volunteers early clinical tests with a small number of patients are done under careful medical supervision if the drug seems to be effective then tests on a larger scale conducted by teams of physicians and psychologists are begun it is only after these many tests have been successfully completed that the drug may be released for public use as we know psychoactive drugs may do great good the treatment of the mentally ill has improved enormously since their development but these drugs do not in themselves affect a cure they may help to create conditions which are favorable to a cure conditions in which the patient through his own efforts and with the assistance of a skilled physician may show major improvement but let's leave the medical aspects of drugs now and consider them in relation to basic research in psychology what we have been discussing so far is the relation between drugs and behavior whether the behavior was on the part of animals or human subjects it just happens that in the demonstrations you saw all animals had received a drug which depressed behavior different drugs would have caused different effects in actual tests we record the animal's behavior at regular intervals of time we see how quickly the drug has its maximum effect when the effect begins to diminish and when recovery is complete in other words we draw a curve of how behavior changes with time meanwhile we run a series of chemical analyses so that we know how much of the drug is in the system at any particular time this too can be plotted as a curve the interesting fact is that in many instances these two curves do not correspond the maximum effect upon behavior may even appear after the drug has been completely eliminated from the body the only kind of event which could possibly account for this discrepancy between the presence of the drug and the change in behavior are the biochemical events which intervene between the drugs and the behavior we have very strong evidence that this is in fact the sequence of events this is microphotography you are looking at a culture of brain cells actually these are animal brain cells there are billions of cells in the brains of higher animals including man cells of several kinds each of them is so to speak a chemical factory constantly performing a whole series of biochemical events now what happens to these particular kinds of cells when a tranquilizing drug is administered clearly it speeds up contraction we can see that it is having an effect upon each individual cell something must be happening to the biochemical events within each cell how do these biochemical events in the cell in turn affect behavior in this experiment i'd like to show how drugs influence specific biochemical events in the brain and they in turn affect behavior this is a normal undrugged rat he is learning to avoid a mild shock on the floor of the cage a shock which occurs within 10 seconds after this platform has been inserted he will avoid the shock by jumping onto the platform within the 10 seconds as you see he waits then he jumps within the time limit [Music] he made the correct response and avoided the shock now that we've established the response we're going to change the rules of the game when the platform is inserted and the animal jumps onto it he'll receive a mild shock on the platform itself rather than on the floor of the cage a normal undrugged animal will respond to this by jumping back to the floor and as soon as he finds that now he does not get a shock from the floor he'll remain there and will not jump back onto the electrified platform the second animal has been given a drug an organic phosphorus compound that has a very specific effect upon an enzyme in the brain this enzyme called cholinesterase is very vitally concerned with nerve transmission what we have done is by giving this drug reduce the level of activity of that enzyme by about 65 percent now we want to see how that change in enzyme activity is related to the animal's behavior we're going to treat the second animal in exactly the same way we did the first one the normal undrugged animal he will first learn how to make the conditioned response and you can see here that he has in fact learned to do so in other words this very significant change in brain cholinesterase activity level has not influenced his ability to learn the response in the first place now let's see if this drugged rat can adapt to the new situation we'll electrify the platform will he jump down to the floor he does but will he stay there no back to the electrified platform [Music] then down to the floor again will he stay this time no back to the platform in the shock and if we were to follow this animal through as many even as 50 trials we'd see that he continued to make this response which he had learned initially but which is no longer adequate to adapt to his changed environment in essence what we've done by changing this particular biochemical event in the brain is to affect the capability of the animal to make an adequate and normal adaptation to its environment now you've just seen the effects of biochemical changes on behavior when drugs produce specific effects upon biochemical events we refer to these effects as biochemical lesions such lesions are not always dependent upon drugs they may occur naturally when they occur naturally they are usually genetically determined and we refer to them as genetic faults in the individual's biochemistry this child for instance has an inherited disease called phenylketonuria pku for short he was born with a biochemical lesion an essential enzyme is missing in the body and corresponding abnormalities and behavior occur as you can see this little girl was also born with pku but look at the contrast in the 1950s a simple chemical test for infants made early diagnosis possible as a result through a rather simple control of diet this child recovered from her biochemical lesion and today behaves in a normal way i think you will now understand what i mean when i say that we are interested in the biochemical correlates of behavior but let me go a step further we are not only interested in what the events are we are also interested in learning as precisely as possible of where the events occur now this is the kind of problem with which my colleague at the state university of iowa dr sebastian grossman is particularly concerned over the past decades scientists have discovered several specific areas of the brain which seem to control man's motivation if we take a cross-section of this brain right here we can have a closer look at some of these areas sexual behavior fear and aggression seem to be controlled at least in part by this area of the brain hunger and thirst seem to be regulated by this portion in the past we have investigated these areas by observing the effects of electrical stimulation we are now interested in investigating the effects of drugs placed directly into these specific areas of the brain if we swallow a drug it will flood the entire organism and we won't know precisely where it produces its effect even if we inject it directly into the brain the force of the injection will spread it over a relatively large area to solve this problem i have developed a cannula like this one which permits the application of very small chemical crystals directly into specific areas of the brain in this animal we have implanted cannula into the region believed to be responsible for the regulation of hunger and thirst inside this cannula is another tube which can be removed you see that this is a completely painless procedure the rat does not object at all this rat has eaten and drunk all it desires and couldn't be less interested in eating or drinking as you see he ignores both the food and the water now we're going to place a small crystal of a chemical into the tip of the inner tube of this cannula the crystal at the tip would slowly dissolve and the chemical begins to stimulate nerve cells which regulate his motivation to eat the drug will spread only this far we thus know precisely where it will be acting to produce the effects which we will observe now let's see how the behavior of this completely satiated animal is affected as you see his interest in food has suddenly returned moreover if we now place him into a situation where he must work for his food he will do so this animal has learned to press this bar for food and this one if he wants a drink of water a short time ago this rat showed no interest in eating now he goes to some trouble to obtain food this reaction is elicited only by a specific chemical let's place another drug into the same spot of the brain now the rat begins to drink and he presses the bar which releases water we have also found drugs which selectively abolish feeding and drinking behavior in animals which are quite hungry or thirsty we see then that behavior is determined by specific chemical action within particular areas of the brain now you might think that this may very well be true for hunger and thirst but that we can't really generalize it to other kinds of behavior i think we can and will give you another example of specific chemical action within another portion of the brain we're going to put a drug into that area of the brain of this cat which regulates aggressive behavior and fear the behavior changes and one cannot even come near the cat which was so friendly just minutes ago when we administer another drug the cat returns to normal so far we have shown that drugs have differential effects upon behavior and that these effects are related to biochemical events which as dr grossman has pointed out occur in specific sites but i should not give the impression that this is a simple one-way causal relationship in fact changes in behavior may precede changes in biochemical events many people are aware of odd feelings in their stomachs when they're under stress now we're interested in measuring the biochemical events which accompany these feelings an electrode like this is attached to the abdomen of the subject it records his gastrointestinal activity generally called just gi activity you can't feel anything because we're only picking up the slight electric current from your own skin we're not putting anything into you does that feel comfortable yeah that's fine there's no no no you won't get any shot you just lie quietly as you see there are two subjects in the room they are simply resting on their cots they have been instructed to remain absolutely inactive during this experiment in the next room are the two recorders which are hooked up to the two electrodes now these are fairly typical patterns of gi activity for relaxed subjects [Music] but now the behavioral situation is being changed an aversive stimulus has been introduced the unpleasant sound which you just heard will be repeated at fixed intervals the man at the left can do absolutely nothing about this sound but the man on the right has at least the possibility of control if he presses his button just before the sound is scheduled to come through the loudspeaker he'll prevent it from going off for the one time but this is an extremely difficult task all the man knows is that the noise recurs at fixed intervals he doesn't know what these intervals are and he has no watch or other aid for keeping track of the time besides he gets only one chance during each trial if he presses the button too early pressing it again will have no effect the recorder on the left displays the gi activity of the men on the left this is the man who has no control over the situation the pattern has stayed about the same despite the periodic noise but the recorder on the right shows a marked increase in gi activity this is the subject who has some degree of control over the aversive stimulus both subjects experience the same experimental stress but it is the decision maker who suffers the psychological stress and therefore he is the one who gets the significantly greater biochemical changes similar experiments have been conducted using monkeys as subjects when they were continued over a period of several weeks the monkey in the decision-making role developed ulcers of course that can't happen to our human subjects because they participate in the experiment for only a very few minutes now we have seen how behavior may influence biochemical events let us now work in the opposite direction again and introduce a drug a tranquilizer here is the capsule that we told you about we'd like you to take this capsule before we do any more recording you have nothing to worry about there's nothing in this capsule that can hurt you so just go ahead and take it first a capsule is given to the decision maker under the direction of a physician but we have to take into account the so-called placebo effect that is the response to suggestion sometimes the subject gets a real drug sometimes a totally inactive substance he doesn't know which nor does the person who gives it to him this is called a double blind technique thus it is possible to distinguish the real effects of a tranquilizer the gi activity of the subject decreases almost back to the level it was at before the stress of having to make difficult decisions was introduced in other words we can modify behavior and thus influence biochemical events or we can use drugs to influence biochemical events which in turn influence behavior biochemical events and behavior are closely linked this is why we can speak of the biochemical correlates of behavior as you know psychoactive drugs have untold value in the treatment of mentally ill i think you can now see why they are also immensely valuable as research tools the chemistry of behavior remains in part an unknown formula but experiments such as these are bringing us closer to the full answer to find this answer to discover the link between drugs body chemistry and behavior remains a challenge to psychologists and to other biological scientists [Applause] so so [Applause] [Applause] this is n-e-t national educational television you