Sleep, behavior, pharmaceutical correction

Sleep is a physiological state that is characterized by the loss of active mental connections of the subject with the world around him. Sleep is vital for higher animals and humans. For a long time, sleep was considered to be the rest necessary to restore the energy of brain cells after active wakefulness. However, it turned out that brain activity during sleep is often higher than during wakefulness. It was found that the activity of neurons in a number of brain structures during sleep increases significantly; sleep is an active physiological process. 

Reflex reactions during sleep are reduced. A sleeping person does not react to many external influences if they are not excessively strong. Sleep is characterized by phase changes in GNI, which are especially pronounced during the transition from wakefulness to sleep (egalitarian, paradoxical, ultra-paradoxical and narcotic phases). In the narcotic phase, animals cease to respond with a conditioned reflex reaction to any conditioned stimuli. Sleep is accompanied by a number of characteristic changes in autonomic parameters and bioelectrical activity of the brain. 

Low-amplitude high-frequency EEG activity (beta rhythm) is characteristic of the state of wakefulness. When the eyes are closed, this activity is replaced by the alpha rhythm, a person falls asleep. During this period, awakening occurs quite easily. After a while, “spindles” begin to appear. After about 30 minutes, the “spindle” stage is replaced by a stage of high-amplitude slow theta waves. Awakening to this stage is difficult, it is accompanied by a number of changes in autonomic parameters: the heart rate decreases, blood pressure, body temperature, etc. decrease. 

The stage of theta waves is replaced by a stage of high-amplitude infraslow delta waves. Delta sleep is a period of deep sleep. Heart rate, blood pressure, body temperature in this phase reach their minimum values. The slow-wave stage of sleep lasts 1-1.5 hours and is replaced by the appearance on the EEG of low-amplitude high-frequency activity characteristic of the state of wakefulness (beta rhythm), which is called paradoxical, or fast-wave, sleep. Thus, the entire period of sleep is divided into two states, which replace each other 6-7 times during the night: slow-wave (orthodox) sleep and fast-wave (paradoxical) sleep. If you wake up a person in the phase of paradoxical sleep, then he reports dreams. A person who wakes up in a phase of slow wave sleep usually does not remember dreams. If a person is selectively deprived of only the paradoxical phase of sleep during sleep, for example, to wake him up as soon as he enters this phase, then this leads to significant disturbances in mental activity. 

Sleep theories. The humoral theory considers substances that appear in the blood during prolonged wakefulness as the cause of sleep. The proof of this theory is an experiment in which an awake dog was transfused with the blood of an animal deprived of sleep for a day. The recipient animal immediately fell asleep. Currently, it has been possible to identify some hypnogenic substances, for example, a peptide that induces delta sleep. But humoral factors cannot be considered as the absolute cause of sleep. This is evidenced by observations of the behavior of two pairs of unseparated twins. Their nervous system was completely divided, and the circulatory systems had many anastomoses. These twins could sleep at different times: one girl, for example, could sleep, while the other was awake. 

Subcortical and cortical sleep theories. With various tumor or infectious lesions of subcortical, especially stem, brain formations, patients have various sleep disorders – from insomnia to prolonged lethargic sleep, which indicates the presence of subcortical sleep centers. When the posterior structures of the subthalamus and hypothalamus were stimulated, the animals fell asleep, and after the cessation of stimulation they woke up, which indicates the presence of sleep centers in these structures. 

In the laboratory of I.P. Pavlov it was found that with prolonged development of fine differential inhibition, animals often fell asleep. Therefore, the scientist considered sleep as a consequence of the processes of internal inhibition, as in-depth, diffuse, inhibition spreading to both hemispheres and the nearest subcortex (cortical theory of sleep). 

However, a number of facts could not explain either the cortical or subcortical theory of sleep. Observations of patients who lacked almost all types of sensitivity showed that such patients fall into a state of sleep as soon as the flow of information from the acting senses is interrupted. For example, in one patient of all the senses, only one eye was preserved, the closing of which immersed the patient in a state of sleep. Many questions of the organization of sleep processes were explained with the discovery of the ascending activating influences of the reticular formation of the brain stem on the cerebral cortex. It was experimentally proved that sleep occurs in all cases of elimination of the ascending activating influences of the reticular formation on the cerebral cortex. The descending influences of the cerebral cortex on subcortical formations were established. In the waking state, in the presence of ascending activating influences of the reticular formation on the cerebral cortex, neurons in the frontal cortex inhibit the activity of neurons in the sleep center of the posterior hypothalamus. In the state of sleep, when the ascending activating effects of the reticular formation on the cerebral cortex decrease, the inhibitory effects of the frontal cortex on the hypothalamic sleep centers decrease. 

There is a reciprocal relationship between the limbic-hypothalamic and reticular structures of the brain. When the limbic-hypothalamic structures of the brain are excited, inhibition of the structures of the reticular formation of the brain stem is observed and vice versa. During wakefulness due to the flow of afferentation from the sense organs, the structures of the reticular formation are activated, which have an upward activating effect on the cerebral cortex. At the same time, the neurons of the frontal cortex have a descending inhibitory effect on the sleep centers of the posterior hypothalamus, which eliminates the blocking effects of the hypothalamic sleep centers on the reticular formation of the midbrain. With a decrease in the flow of sensory information, the ascending activating effects of the reticular formation on the cerebral cortex decrease. As a result, the inhibitory effects of the frontal cortex on the neurons of the sleep center of the posterior hypothalamus are eliminated, which begin to inhibit the reticular formation of the brainstem even more actively. Under conditions of blockade of all ascending activating influences of subcortical formations on the cerebral cortex, a slow-wave stage of sleep is observed. 

Hypothalamic centers, due to connections with the limbic structures of the brain, can exert upward activating effects on the cerebral cortex in the absence of influences from the reticular formation of the brainstem. These mechanisms constitute the cortical-subcortical theory of sleep (P.K. Anokhin), which made it possible to explain all types of sleep and its disorders. It proceeds from the fact that the state of sleep is associated with the most important mechanism – a decrease in the ascending activating influences of the reticular formation on the cerebral cortex. The sleep of crustless animals and newborns is explained by the weak severity of the descending influences of the frontal cortex on the hypothalamic sleep centers, which under these conditions are in an active state and have an inhibitory effect on the neurons of the reticular formation of the brain stem. 

The sleep of the newborn is periodically interrupted only by the excitement of the center of hunger, located in the lateral nuclei of the hypothalamus, which inhibits the activity of the sleep center. This creates conditions for the entry of the ascending activating influences of the reticular formation into the cortex. This theory explains many sleep disorders.
Insomnia, for example, often occurs as a consequence of overexcitation of the cortex under the influence of smoking, strenuous creative work before bedtime. At the same time, the descending inhibitory effects of the neurons of the frontal cortex on the hypothalamic sleep centers are enhanced and the mechanism of their blocking action on the reticular formation of the brain stem is suppressed. Prolonged sleep can be observed when the centers of the posterior hypothalamus are irritated by a vascular or tumor pathological process. Excited sleep center cells continuously block the neurons of the reticular formation of the brainstem. 

Sometimes during sleep, the so-called partial wakefulness is observed, which is explained by the presence of certain channels of reverberation of excitations between the subcortical structures and the cerebral cortex during sleep against the background of a decrease in the ascending activating influences of the reticular formation on the cerebral cortex. For example, a nursing mother may sleep soundly and not respond to strong sounds, but she quickly wakes up even with little movement of the baby. In the case of pathological changes in one or another organ, increased impulses from it can determine the nature of dreams and be a kind of harbinger of a disease, the subjective signs of which are not yet perceived in the waking state. 

Pharmacological sleep is inadequate in its mechanisms to natural sleep. Sleeping pills limit the activity of various brain structures – the reticular formation, the hypothalamic region, and the cerebral cortex. This leads to disruption of the natural mechanisms of the formation of sleep stages, disruption of the process of memory consolidation, processing and assimilation of information. 

Functional system of behavior

The degree of complexity and nature of the components of behavioral acts may be different, but their fundamental organization is the same. Modern physiology considers all behavioral acts from the standpoint of the theory of functional systems of P.K. Anokhin (Fig. 1). 

According to this theory, during the implementation of a conditioned reflex, the stimulus acts against the background of prestarting integration, which is formed on the basis of various types of afferent excitations. Ambient afferentation is the sum of afferent excitations that arise in specific conditions and signal the environment in which the body is located. Ambient afferentation acts on an organism in which there is one or another level of motivational arousal (motivation). The dominant motivation is formed on the basis of the leading need, with the participation of the motivational centers of the hypothalamus. At the stage of afferent synthesis, the dominant motivation activates memory. 

The significance of memory at the stage of afferent synthesis is that it extracts information related to the satisfaction of the dominant motivation. These three types of excitations: motivational, memory, and situational afferentation create pretrigger integration, against the background of which the fourth type of afferentation acts – triggering afferentation (triggering stimulus, conditioned signal). These four types of excitations interact and provide the formation of the first stage of the functional system of behavior – afferent synthesis. The main condition for the formation of afferent synthesis is the meeting of all four types of afferentations, which are processed simultaneously due to the convergence of all types of excitations. The stage of afferent synthesis provides a goal setting, the achievement of which will be devoted to the entire implementation of the functional system.

 Decision making (goal setting) is the second stage and is carried out only on the basis of complete afferent synthesis. Thanks to the decision-making, a form of behavior is adopted that corresponds to the internal need, the previous experience and the environment, which allows you to carry out exactly the action that should lead to the programmed result. 

The third stage is the formation of an action program. At this stage, ways of realizing a specific goal are provided, efferent commands to various executive bodies are formed. At the same time, a special apparatus is created in neural structures – an acceptor of the result of an action, which predicts all parameters of a future result. 

The formation of the acceptor of the results of action is the fourth stage in the creation of a functional system. It must provide mechanisms that allow not only to predict the parameters of the required result, but also to compare them with the parameters of the actually obtained result. Information about them comes to the acceptor thanks to inverse afferentations, which allows you to correct a mistake or bring imperfect behavioral acts to perfect ones. The acceptor of the results of an action is an ideal image (standard) of future results of an action. Excitations of not only afferent but also efferent nature come to this nervous complex. Collateral branches of the pyramidal tract through a chain of intermediate neurons withdraw some of the efferent commands going to the effector. 

These excitations converge to the same intermediate neurons of the sensorimotor cortex, where afferent excitations arrive, transmitting information about the parameters of the real result. If the results do not correspond to the prediction, then a mismatch reaction occurs, activating an orientation-exploratory reaction, which increases the associative capabilities of the brain, providing an active search for additional information. 

On its basis, a new, more complete afferent synthesis is formed, a more adequate decision is made, which, in turn, leads to the formation of a more perfect action program, which allows one to obtain the desired result. The neurons involved in the formation of the functional system are located in all structures of the central nervous system, at all its levels. When the desired beneficial result is achieved, an agreement reaction is formed in the acceptor of the action results, an afferentation arrives, signaling the satisfaction of motivation. This is where the functional system ceases to exist. 

The processes of agreement or mismatch that arise when comparing the parameters of the actually obtained result with the programmed in the acceptor of the results of action are accompanied either by a feeling of satisfaction or dissatisfaction, i.e. positive and negative emotions. 

Pharmacological agents affecting mental activity

By acting on the mediator systems of various parts of the brain with psychotropic drugs, it is possible to cause not only an increase or inhibition of excitatory and inhibitory processes, but also changes in the psyche, mental performance and emotional behavior of the patient. The group of psychotropic drugs includes: 1) neuroleptics (antipsychotics); 2) tranquilizers; 3) sedatives; 4) antidepressants; 5) lithium preparations; 6) nootropic drugs; 7) psychostimulants. 

Antipsychotics have a calming effect with a decrease in response to external stimuli, weakening of psychomotor agitation and tension. They suppress feelings of fear, delusions, hallucinations. The mechanism of action of antipsychotics is based on their inhibitory effect on the reticular formation and its activating effect on the cerebral cortex, as well as on the interaction of antipsychotics with the mediator systems of the brain: adreno-, serotonin-, choline-, GABA- and especially with dopaminergic ones. 

The antipsychotic activity of neuroleptics (aminazine,
levomepromazine) is due to their inhibitory effect on noradrenergic receptors, on dopamine receptors of the substantia nigra, striatum, and limbic system of the brain (fluorophenazine, haloperidolidr.). 

Tranquilizers (from the Latin tranquilloare – to make calm, indifferent) are used mainly for neuroses to eliminate emotional tension, anxiety and fear. In addition to the antiphobic, they have hypnotic, muscle relaxant and anticonvulsant effects. Tranquilizers reduce the excitability of the subcortical structures of the brain (limbic system, thalamus, hypothalamus) and inhibit the interaction between these structures and the cerebral cortex. In addition, these drugs inhibit polysynaptic spinal reflexes and induce muscle relaxation. In medical practice, such drugs of this group as Elenium (Chlosepid), Diazepam (Relanium), Phenazepam, Amizil, Mebikar, etc. have found application. 

Sedatives have a less pronounced sedative and anti-phobic effect than tranquilizers, do not cause muscle relaxation. They have a regulatory effect on the processes of excitation and inhibition in the brain and are used in outpatient practice for the treatment of mild neurotic conditions. These include, first of all, herbal preparations (from the root of valerian, motherwort). 

Antidepressants are drugs that have a positive effect on the mood and overall mental state of the patient. In depressive states, there is a decrease in the activity of noradrenergic and serotonergic synaptic transmission. Therefore, the action of antidepressants is based on their inhibition of monoamine oxidase (MAO), an enzyme that inactivates monoamines (norepinephrine, dopamine, serotonin). Suppression of MAO activity leads to the accumulation of monoamines and an improvement in synaptic transmission in brain structures. These drugs include: nialamide, pi-razidol, befol, etc. 

In addition, there are antidepressants – inhibitors of neuronal reuptake selectively or norepinephrine, or serotonin, or dopamine (azafen). 

Lithium preparations (lithium carbonate, lithium oxybutyrate) are widely used for the treatment of endogenous affective diseases, for the relief of acute manic excitement in mental patients. In large doses, lithium lowers the content of serotonin in the brain and increases the sensitivity of neurons in the hippocampus and other areas of the brain to the action of dopamine, affecting neurochemical processes in the nervous tissue. 

Nootropic drugs (piracetam, aminalon, sodium oxybutyrate, phenibut, etc.) are a group of drugs that have a specific activating effect on the integrative activity of the brain, improve memory, learning and cognitive activity, facilitate the transfer of information between the cerebral hemispheres, increase the brain’s resistance to hypoxia … 

Due to the fact that the main representative of this group of drugs, piracetam, is a synthetic analogue of the inhibitory mediator GABA, it must be assumed that piracetam is able to enhance inhibitory processes in the brain. In addition, this drug enhances the synthesis of dopamine and increases the level of norepinephrine, some nootropics increase the content of acetylcholine and serotonin in the nervous tissue. A feature of nootropics is their stimulating effect on metabolic and bioenergetic processes in nerve cells. 

Nootropics are used to stabilize impaired brain functions in mental illness, in the elderly and in children, to treat vascular and metabolic disorders of the brain. 

The group of psychostimulants of the central nervous system, in addition to analeptics and drugs acting on the spinal cord, includes psychomotor stimulants (caffeine, phenamine, etc.), which activate the bioelectrical activity of the brain, increase physical and mental performance, reduce fatigue and drowsiness. The mechanism of action of these drugs is associated with their ability to stimulate the synthesis of cyclic AMP, which is involved in all metabolic processes.

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