To be able to understand how psychopharmaca works (the pharmaca that effect our brains thereby influencing the mind), it is necessary to have some insight into the structure of the brain.
So, first something about the brain.
The brain is often compared to a computer.
One common denominator is, for example, that in both information processing systems the information is sent by electrical impulse.
However, the elements that make up a computer are connected to each other: the computer is a continuous system.
Our brain, on the other hand, is made up of nerve cells, neurons, which are not connected to each other: our brain is discontinuous.
The brain has about 10,000,000,000 of these neurons as well as many more supporting cells, called glial cells.
Each nerve cell is connected to approx. 10,000 others and together they form a network which makes even the most advanced supercomputer seem a mere rudiment.
Neurons consist of a cell body with a long process (called an axon) that makes contact with the dendrites of other neurons. See fig. 1
What is special about neurons is that there is a potential difference between the inside and the outside of the cell resulting from differences in the concentration of the sodium ions and the potassium ions.
The chief extracellular ion is sodium, the chief intracellular ion, potassium.
Disruption of this pattern results in a change in the potential difference.
This disruption rushes like a wave along the surface of the neuron. This disrupted conduction is called an action potential. Action potentials are conducted along the long processes of the neurons, the axons, and transfer messages in this way. When an action potential reaches the end of the axon, an impulse does not jump over to the dendrite, but releases a chemical stored in a little sac at the end of the axon.
This chemical, a neurotransmitter, passes the presynaptic membrane, pushes through the narrow cleft between the axon and the dendrite of the next neuron, the synaps, and reacts with special molecules in the cell wall of the next neuron.
These molecules are receptors located in the postsynaptic membrane.
Each nerve cell has about 10,000 synapses, a number of which are always active.
This activity continually causes such disturbances in that tension difference. In each case when the result of all these disturbances go beyond a specific limit, the neuron generates a new action potential which is then transmitted along the process of that cell to the next synapses.
After the neurotransmitter has ‘opened the gates’, it is thrust from the receptor and either broken down or taken up again in the axonal terminal for re use.
This latter process is called re uptake.
Chemicals that block re uptake intensify the effect of the neurotransmitter because they remain in the synaptic cleft and continue to stimulate the receptors.
The neuron is, thus, a kind of small calculator that can only add (if the imbalances reinforce each other) or subtract (if the imbalances work against each other) and in this can be compared with a transistor in a computer.
An example might clarify this process.
Everyone knows about the kneejerk reflex: a tap on the knee tendon makes a bent knee contract. The underlying mechanism is that the hammer tap on the knee tendon stimulates a signal in that tendon whereby one or a series of action potentials are passed on along the nerve to a synaps in the spinal cord.
The neurotransmitter released there stimulates another neuron whose process sends the action potential to the upper leg muscles which then contract and extend the leg.
Although it is easy for the doctor to elicit this reflex, it is difficult to elicit in oneself.
This is because the concentration needed by an individual to elicit the reflex is also in the form of a series of opposing action potentials originating from the cerebellum, traveling along this same spinal cord cell and canceling the effect of the action potentials from the knee tendon nerve; no, or very few action potentials get to the upper leg muscles, the leg remains bent.
That communication between neurons is a result of the release of chemicals was possibly first put forward by the British physiologist Thomas Elliot in 1905, but pointers were discovered by Otto Loewi in 1921.
He put a frog’s heart in a salt solution which kept it beating, and let the fluid flow through a second frog’s heart. He then stimulated the first heart’s nervus vagus, the nerve that slows down the heart. As expected, the heart started beating slower, however, quite unexpectedly the second heart also started beating slower without stimulation of the nervus vagus of that heart.
So a chemical must have been released from the nervus vagus of the first heart which combined with and influenced the perfusion fluid in the second heart. This chemical was later identified by Sir Henry Dale as acetylcholine.
As mentioned earlier, the reaction between neurotransmitter and receptor is very specific.
Initially it was thought that there were only several neurotransmitters; acetylcholine and a number of organic ammonia compounds, the biogenic amines: adrenalin, noradrenalin, serotonin, dopamine and histamine.
Then it seemed that a number of amino acids (the building blocks of proteins) also function as neurotransmitters of which gamma amino butyric acid and glycine are the most important.
Finally, in the Seventies it became clear that a number of peptides (small amino acid chains) also fulfilled this function.
More than thirty chemicals have by now been identified as neurotransmitters and many more are expected to be identified.
There are also chemicals that do not function directly as neurotransmitters, but influence the working of the neurotransmitters (the neuromodulators) by their effect on e.g. neurotransmitter metabolism.
Finally, it is possible that nerves also separate chemicals that do not end up in a synaptic cleft but in the blood or in the free extracellular space and then act as a hormone.
All psychopharmaca have their effects because they influence neurotransmission by the synapse in some way. They can do this in various ways.
First the production, the synthesis, of theneurotransmitter can be stimulated by administering its building blocks.
Next, the neurotransmitter is stored (storage) in small sacs. Drugs can have an effect on this; the most clear example here is the drugs that break open the sacs that protect the transmitter against enzymes which are breaking down, so that these enzymes destroy the transmitter and the effect of the neurotransmitter concerned is lost.
The third phase is separation in the synaptic cleft: the release. Some drugs enhance separation or have the opposite effect and inhibit it, which results in either an increased or reduced effect.
The fourth phase is stimulation of the receptor: psychopharmaca often imitates the neurotransmitter by stimulating the receptors itself.
After having stimulated the receptor, the neurotransmitter returns to the synaptic cleft.
Two things can happen here: either enzymatic breakdown of the neurotransmitter or re uptake takes place.
In re uptake, the neurotransmitter molecules are taken up again by the presynaptic neuronfor re use. Drugs can either enhance or block both breakdown and re uptake.
Finally, there are drugs that interfere with the intracellular mechanism after stimulation by a neurotransmitter, thereby blocking or enhancing the effect. This is then manipulation ofthe post receptor mechanisms.
Our nervous system evolved from a simple string of nerve cells that could only bring about the simplest reflex movements such as e.g. in the lancelet. This tiny animal is about the simplest vertebrate and is not much more complicated than a worm. At the other end of this developmental line is the human with the most complicated nervous system. The most important principle underlying this development is that new elements are continually being added to the existing system; they do not displace it. Quite the reverse in fact, as the older elements are, as it were, manipulated by the newly evolved higher elements. Our nervous system consists of superimposed control circuits that continually make more complicated behavior possible.
A distinction is made between two subdivisions: the central nervous system (CNS), which consists of the brain and spinal cord, and the peripheral nervous system (PNS), that part of the nervous system outside the CNS which consists mainly of the nerves that extend from the CNS.
Another distinction made is of functional character, namely between the voluntary and the involuntary nervous systems. The first allows us to control our skeletal muscles consciously. The second, also called the autonomic nervous system (ANS), regulates all events not under conscious control: the activity of the internal organs, such as the heart, stomach, etc. The ANS itself has two parts: the sympathetic part that activates, and the parasympathetic part that de-activates.
The central nervous system is built up of the following parts:
The ‘simplest’ part of our nervous system is the spinal cord. In theory, it can still be compared with the nervous system of the lancelet. As noted earlier, the kneejerk reflex travels along the spinal cord. All our motor activity happens by manipulation of such reflex centers by the higher nerve centers. All communication with the brain travels through the spinal cord. Two thick tracks of axons run from the brain to these reflex centers for motor control: the pyramidal tracts. In addition, thick bundles of axons travel to the brain from the sensory receptors in the skin, muscles, etc. and control sensory input of the brain.
This is actually the first part of the original brain stem that continued to develop because the most important sensory organs (in order of their evolutionary development: for smell, taste, vision and hearing) are localized at the front side of the body. Information processing from these organs led to continual enlargement of the brain.
Control of the vital functions is organized in the brain stem. This is where breathing and blood pressure are regulated; where the awake/sleep cycle is regulated. All (passive) vital functions necessary to stay alive are controlled from here.
Little brain (Cerebellum)
The cerebellum plays an important role in body movement. While the brain stem can only regulate simple reflexes ‘independently’, in the cerebellum complicated patterns of movement, ‘movement melodies’, are initiated and stored as fixed patterns. The cerebellum is present even in primitive fish and its importance increases along the evolutionary scale. The more complicated the motor activity of an animal, the larger the cerebellum.
The limbic system can best be described as the first beginning of the great brain. Research has given us some idea of how this system works. Both the nature and the results of such research can best be illustrated by the following famous example. The Spanish neurophysiologist DEGADO planted electrodes into a specific part of the limbic system of a Spanish fighting bull and fitted it with a receiver so that when a signal was sent by a transmitter a current would flow through one of the electrodes and stimulate the cells concerned. Once the wound from the operation had healed, the bull was taken to the arena and, in the traditional way, provoked fury by the toreadors. Delgado then entered the arena and provoked the bull which then charged him, head down to take Delgado on his horns.
When the bull was only a few meters away from Delgado, he pressed the button of the transmitter in his pocket which stimulated the bull’s brain and the bull calmed down immediately. Efforts by the toreadors to enrage the bull again were unsuccessful as long as Delgado kept stimulating the bull’s brain. Only by pressing another button which stimulated a different part of the limbic system could the bull again be brought to a state of rage without the help of the toreadors. Evidently, the cells in which Delgado planted his electrodes requlate rage and tranquillity. The cells concerned are part of the limbic system and are found in the amygdaloid body, the amygdala. In a way similar to this rats and other animals can, by selective stimulation of other parts of the limbic system, be motivated to eat, resp. refuse food, to sexual arousal resp. be made immune to the usual sexual stimulations. In short, the limbic system regulates a number of very vital emotions. This effect can also be elicited in humans:
‘The first time we were able to demonstrate that systems in the limbic brain that both start and stop attack behaviour was with patient Thomas R. Thomas’ chief problem was his violent rage…. NOTE 2 Electrodes were implanted in his amygdala and the daily stimulation of specific parts of it (the lateral) kept him free from attacks of rage for two months. Since it is not possible to continue this regimen throughout a patient’s life, those parts of his amygdala which elicited an attack of rage when stimulated (the medial) were destroyed electrically. His attacks of rage subsequently stopped. This operation was, incidentally, thereason for a lawsuit between the two neurosurgeons and the mother of Thomas R. who had fought the operation NOTE 3 . The court’s decision is unknown to the author.
In this connection it is striking that disorders in these regulating mechanisms lead to behavioral disorders which, though not necessarily seen by all as addictions, are nevertheless seen as ‘cravings’: bulimia, anorexia nervosa, gambling fever, etc. We may assume that the addictive effect of some drugs is connected with their influence on the receptors in the limbic system.
Furthermore, the limbic system influences the hormonal system by means of the hypophysis (pituitary gland), a small gland attached to the base of the brain. Finally, the limbic system, especially that part to do with the hippocampus, plays a very important role in memory.
The limbic system is already somewhat developed in fish and reaches full development in the reptiles. In rudimentary form its main function is processing olfactory stimuli; later, this function shifts to regulating emotions. An echo of this old function can be seen in the fact that no sensory stimulation can elicit stronger emotions than a smell. The human limbic system is virtually no different than that of the reptiles. It represents the ‘crocodile’ in us.
These are the communication stations between the brain stem and the limbic system on the one hand and the cerebral cortex on the other. The complicated behavior patterns are organized here. In this connection an important part of these centers, which some think are a part of the limbic system, is the nucleus accumbens.
The role these centers play becomes clear with experiments in which laboratory animals with a permanently implanted electrode or a permanent infusion stimulate themselves by pressing a button. When such an electrode is implanted in the nucleus accumbens, and the laboratory animal realizes that the sensation it is getting is caused by pressing the button, the feeling is so pleasurable that the animal will lie down on the button. Other locations in this center have the reverse effect. The theory now is that this center functions as a kind of punishment/reward center in the sense that eating when you are hungry also stimulates the reward center, while with satiation the punishment center is stimulated if you then continue to eat. Stimulation of this center could, then, give a feeling of reward, without there necessarily being any ‘rewardable’ behavior. Why should you eat, drink, have sex, etc. if you can also elicit the ultimate feeling of reward by electrode (or by a needle in your arm)?
These subcortical centers, together with some parts of the cerebral cortex which other mammals also have, can be referred to as the ‘horse ‘ in us.
Cortex cerebri (the cerebral cortex)
The cerebral cortex is the most complicated part of the nervous system. It is divided into four parts: the frontal lobe, the parietal lobe, the temporal lobe and the occipital lobe. All sensory perceptions are ‘projected’ onto the cerebral cortex and the outside world is represented by these projection fields. For example, each point in the visual field is represented by a point in the visual projection field in the occipital lobe. This is, incidently, where the story comes from that you can go blind if you fall on your tailbone. The shock is conducted along the spinal cord to the back of the head and the skull knocks against the visual projection field. This if damaged, causes blindness although nothing is wrong with the eyes. In the same way, all sounds, from high to low, are represented in the auditory projection field in the temporal lobe, the entire body surface is represented in the sensory cortex in the parietal lobe and all muscles in the frontal lobe. In addition to these projection fields, we also have association fields where the connections between this sensory input and motor output are made. That part of the brain which ‘seats’ language is particularly large even compared with our closest relative, the chimpanzee. In this association field the different aspects of language – hearing, seeing (both objects and letters) and speaking (larynx muscles) coordinate. The slightest damage to this area can lead to abnormalities such as aphasia, dyslexia, etc.
The cerebral cortex is, mainly because of the latter mentioned association field, the ‘knight’ in us. Every psychosocial worker should realize that we are not people, but rather knights sitting on a horse, with the horse standing on a crocodile. We pay close attention to the horse, but if the crocodile in us suddenly turns left or right, we tumble to the ground: we call it a life crisis then.