**6. Ethanol as a psychoactive drug and its effect on neurotransmitters**

Ethanol is a psychoactive substance which is present as the active ingredient in alcoholic beverages such as beer, wine, and distilled spirits [27]. Ethanol consumption produces mood lift and euphoria, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor, and sensory function, and slows down the activity (depressant) of the central nervous system (CNS) and because of its psychoactive effects, it is considered a drug. Psychoactive substances are those substances that act on the nervous system to alter states of consciousness, modify perceptions and change moods. Psychoactive drugs are classified into depressants, stimulants and hallucinogens. Depressants slow down physical and mental activity; Stimulants increases the activity of the central nervous system while Hallucinogens modify perceptions and produce unusual visual images.

Human behaviors and emotions are modulated by neurotransmitters that act as keys between neurons. Ethanol has been shown to affect a variety of neurotransmitters in the CNS. A neurotransmitter is a chemical that helps transmit messages from cell to cell within the nervous system and are crucial to muscle control, influences thought processes, memory and emotion. Alcohol mainly affects the nerve cells in the brain, causing interference between communication of these cells and other cells throughout the body. This interference restrains the activities of the excitatory nerve pathways and increases the activities of inhibitory nerve pathways. Alcohol affects several neurotransmitter systems—those for GABA, glutamate, serotonin and dopamine. Alcohol is an agonist for GABA, serotonin and dopamine—it increases their activity and is an antagonist for glutamate—it reduces glutamate activity.

**43**

**Figure 6.**

*Neuron-neuron interaction—transmission of impulse across the synapse.*

*Ethanol*

to sodium ions (Na+

activation of GABAA receptors.

*DOI: http://dx.doi.org/10.5772/intechopen.79861*

Neurotransmitters interact with receptors on the dendrites of the other neuron and have specific shapes that fit into a receptor that can accommodate that shape. Once the neurotransmitter and the receptor are connected, the neurotransmitter sends information to the next neuron to either fire an action potential, or to inhibit firing (**Figure 6**). Neurotransmitters can either be excitatory or inhibitory according to the effect they have on the second neuron once they are released into the synaptic gap. Excitatory neurotransmitter triggers depolarization, increasing the likelihood of a response while inhibitory neurotransmitter triggers hyperpolarization, decreasing the likelihood of a response. Excitatory and inhibitory synaptic transmission use different neurotransmitters and receptors. Excitatory synaptic transmission uses a neurotransmitter called glutamate. Glutamate is a common amino acid used in the body to build proteins. In the central nervous system, it is the major excitatory neurotransmitter where it interacts with glutamate receptors in the post-synaptic neuron. These receptors are ion channels that are permeable

) and thus generate an action potential. Excitatory synaptic

transmission also uses other neurotransmitter like acetylcholine, nitric oxide and

Inhibitory synaptic transmission uses a neurotransmitter called gamma-amino butyric acid (GABA). This interacts with GABA receptors, ion channels that are permeable to negatively charged chloride ions and opening of these channels makes it harder for a neuron to generate an action potential. Inhibitory synaptic transmission also uses serotonin, glycine and taurine as neurotransmitter. The main inhibitory neurotransmitter in the brain is GABA [28] and two major subtypes of GABA receptor have been described. The GABAA receptor family of ligand-gated ion channels consists of pentameric complexes containing binding sites for GABA agonists and other agent. The GABAA receptor complex regulates chloride ion flux through a coupled chloride channel and ethanol is widely reported to increase the

Ethanol is an indirect GABA agonist and psychotropic depressant of the CNS [29]. This property is associated with the action of alcohol on different neurotransmitters, including the stimulation of gamma-amino butyric acid and the inhibition of glutamate, the main central excitatory neurotransmitter. Alcohol potentiates the effects of GABA by acting directly on its receptors, enhancing their inhibitory effect which includes sedation, loss of inhibitions and relaxation [30]. The mechanism

catecholamines (norepinephrine, epinephrine and dopamine).

### *Ethanol DOI: http://dx.doi.org/10.5772/intechopen.79861*

*Psychology of Health - Biopsychosocial Approach*

Many consumers of alcoholic beverages suffer from various degrees of malnutrition (both primary and secondary malnutrition). A situation where alcohol replaces other nutrients in the diet resulting in overall reduced nutrient intake is known as primary malnutrition while secondary malnutrition occurs when alcoholics consumes adequate nutrients but alcohol interferes with the absorption of those nutrients from the intestine so they are not available to the body [25]. The risk of developing micro- and macronutrient deficiencies increases significantly when alcohol makes up more than 30% of total caloric intake [26]. Heavy alcohol consumption not only influences the drinker's diet but also affects the metabolism of those nutrients that are consumed. Even if the drinker ingests sufficient proteins, fats, vitamins, and minerals, deficiencies may develop if those nutrients are not adequately absorbed from the gastrointestinal tract into the blood, are not broken

Proteins are essential nutrients for the human body that help maintain the cell's structure, act as enzymes that mediate almost all biochemical processes/reactions occurring in the body and transport certain substances in the body. Amino acids are building blocks of proteins and proteins are composed of 20 different amino acids. Some of these amino acids can be made by the body itself (non-essential amino acids) from various precursors or are recycled when proteins that are damaged or are no longer needed are broken down or degraded. Other amino acids cannot be produced by the body and must be obtained through diet (essential amino acids). Heavy alcohol consumption can interfere with the production and uptake of these non-essential and essential amino acids. Vitamins are micronutrients present in food essential for normal metabolism and insufficient levels of vitamin in the body can lead to serious health consequences. Alcoholics tends to have deficiencies in certain vitamins particularly thiamine (vitamin B1), riboflavin (vitamin B2),

down properly, and/or are not used effectively by the body's cells.

pyridoxine (vitamin B6), ascorbic acid (vitamin C) and folic acid.

**6. Ethanol as a psychoactive drug and its effect on neurotransmitters**

Ethanol is a psychoactive substance which is present as the active ingredient in alcoholic beverages such as beer, wine, and distilled spirits [27]. Ethanol consumption produces mood lift and euphoria, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor, and sensory function, and slows down the activity (depressant) of the central nervous system (CNS) and because of its psychoactive effects, it is considered a drug. Psychoactive substances are those substances that act on the nervous system to alter states of consciousness, modify perceptions and change moods. Psychoactive drugs are classified into depressants, stimulants and hallucinogens. Depressants slow down physical and mental activity; Stimulants increases the activity of the central nervous system while Hallucinogens modify perceptions and produce unusual visual images.

Human behaviors and emotions are modulated by neurotransmitters that act as keys between neurons. Ethanol has been shown to affect a variety of neurotransmitters in the CNS. A neurotransmitter is a chemical that helps transmit messages from cell to cell within the nervous system and are crucial to muscle control, influences thought processes, memory and emotion. Alcohol mainly affects the nerve cells in the brain, causing interference between communication of these cells and other cells throughout the body. This interference restrains the activities of the excitatory nerve pathways and increases the activities of inhibitory nerve pathways. Alcohol affects several neurotransmitter systems—those for GABA, glutamate, serotonin and dopamine. Alcohol is an agonist for GABA, serotonin and dopamine—it increases their activity and is an antagonist for glutamate—it reduces glutamate activity.

**42**

Neurotransmitters interact with receptors on the dendrites of the other neuron and have specific shapes that fit into a receptor that can accommodate that shape. Once the neurotransmitter and the receptor are connected, the neurotransmitter sends information to the next neuron to either fire an action potential, or to inhibit firing (**Figure 6**). Neurotransmitters can either be excitatory or inhibitory according to the effect they have on the second neuron once they are released into the synaptic gap. Excitatory neurotransmitter triggers depolarization, increasing the likelihood of a response while inhibitory neurotransmitter triggers hyperpolarization, decreasing the likelihood of a response. Excitatory and inhibitory synaptic transmission use different neurotransmitters and receptors. Excitatory synaptic transmission uses a neurotransmitter called glutamate. Glutamate is a common amino acid used in the body to build proteins. In the central nervous system, it is the major excitatory neurotransmitter where it interacts with glutamate receptors in the post-synaptic neuron. These receptors are ion channels that are permeable to sodium ions (Na+ ) and thus generate an action potential. Excitatory synaptic transmission also uses other neurotransmitter like acetylcholine, nitric oxide and catecholamines (norepinephrine, epinephrine and dopamine).

Inhibitory synaptic transmission uses a neurotransmitter called gamma-amino butyric acid (GABA). This interacts with GABA receptors, ion channels that are permeable to negatively charged chloride ions and opening of these channels makes it harder for a neuron to generate an action potential. Inhibitory synaptic transmission also uses serotonin, glycine and taurine as neurotransmitter. The main inhibitory neurotransmitter in the brain is GABA [28] and two major subtypes of GABA receptor have been described. The GABAA receptor family of ligand-gated ion channels consists of pentameric complexes containing binding sites for GABA agonists and other agent. The GABAA receptor complex regulates chloride ion flux through a coupled chloride channel and ethanol is widely reported to increase the activation of GABAA receptors.

Ethanol is an indirect GABA agonist and psychotropic depressant of the CNS [29]. This property is associated with the action of alcohol on different neurotransmitters, including the stimulation of gamma-amino butyric acid and the inhibition of glutamate, the main central excitatory neurotransmitter. Alcohol potentiates the effects of GABA by acting directly on its receptors, enhancing their inhibitory effect which includes sedation, loss of inhibitions and relaxation [30]. The mechanism

by which ethanol enhances GABAA inhibitory currents involved a hyperpolarizing shift in the GABAA inhibitory postsynaptic current (IPSC) reversal potential in cortex neurons and increasing the amplitude of GABAA receptor-mediated conductance in septal neurons [31]. When GABAA receptor activation is enhanced by ethanol, it may involve enhancement of the initial peak of Cl<sup>−</sup> current through the channel rather than the sustained component of channel opening [32]. The enhancement of the GABAA receptor activation by ethanol may be modulated, in part, by protein kinase C (PKC) [33].

Glutamate is a major excitatory neurotransmitter in the brain that exerts its effects through several receptor subtypes, including the N-methyl-D-aspartate (NMDA) receptor. Unlike the case with GABA, alcohol inhibits glutamate activity in the brain. In a region of the brain called striatum which contains the nucleus accumbens, ethanol exposure causes a drop in the extra cellular glutamate levels [34]. Following acute administration ethanol, glutamate mediated signal transmission is suppressed in the central nucleus of the amygdala and this effect is enhanced following chronic alcohol exposure [35]. Ethanol inhibits ionotropic glutamate, amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors activity in the brain and N-methyl-D-aspartate (NMDA) receptors are the major target of ethanol's inhibitory action. Ethanol also inhibits the induction of neural plasticity in many brain regions including the dorsal and ventral striatum as a result of inhibitory effects on ionotropic receptors, especially the NMDA receptors [36, 37].

Serotonin is a monoamine neurotransmitter known as 5-HT, a derivative of tryptophan and is extensively found in the gastrointestinal tract, platelets and the CNS. Serotonin plays a role in many brain processes, including regulation of body temperature, sleep, mood, appetite, pain and modulates behavioral response to unfairness [38]. Defect with the serotonin pathway can cause obsessive-compulsive disorder, anxiety disorders and depression. Most of the drugs used to treat depression today work by increasing serotonin levels in the brain [39]. Alcohol increases serotonin release in the nervous system. Increase in concentrations of serotonin in the urine and blood have been observed after taking alcohol. Alcohol exposure alters various aspects of serotonin's synaptic functions and also interferes with the function of serotonin receptors including the 5-HT1A, 5-HT1B, 5-HT2, and 5-HT3 receptors. Each subtype of serotonin receptors has its own specific influence on behavior related to the consumption of alcohol [40]. 5-HT1A may control consummatory behavior, including alcohol consumption while 5-HT1B may contribute not only to alcohol's intoxicating effects, but also influence the development of tolerance to alcohol. 5-HT2 plays a role in alcohol's rewarding effects and contributes to the development of alcohol withdrawal symptoms while 5-HT3 has a part in regulating alcohol consumption. Serotonin also affects other neurotransmitters. For example, alcohol-facilitated serotonin may affect the GABA system [41]. Similarly, alcohol-influenced serotonin works to stimulate increased dopamine production and, thus, increased emotional behavior [42].

Dopamine is a neurotransmitter primarily involved in a circuit called the mesolimbic system, which projects from the brain's ventral tegmental area to the nucleus accumbens. It is an excitatory neurotransmitter in the catecholamine family responsible for modulating reward and pleasure. It plays a key role in regulating emotional responses, the reward seeking processes and movement. Several lines of evidence converge to demonstrate that the dopaminergic mesolimbic system plays a significant part in the motivational and reinforcement mechanisms related to behaviors that are vital to survival [43]. Alcohol increases dopaminergic transmission in the mesolimbic pathway and increases the firing rate of dopaminergic neurons, which enhances the amount of dopamine released in the core of the system.

**45**

*Ethanol*

*DOI: http://dx.doi.org/10.5772/intechopen.79861*

results in the kidney producing more urine.

**8. Conclusion**

**Conflict of interest**

I have no conflict of interest to declare.

**7. Effect of ethanol on antidiuretic hormone (vasopressin)**

Vasopressin is an antidiuretic hormone that plays a major role in the regulation of water excretion. The posterior pituitary gland releases vasopressin in response to a fall in blood volume or a rise in plasma osmolality and acts to conserve water by increasing the permeability of water to the distal convoluted tubules and collecting tubules in the renal nephrons through insertion of aquaporin-2 channels into the apical membrane of the tubular epithelial cells [44]. Ingestion of alcohol does increase plasma osmolality, but alcohol also acts directly to inhibit the release of vasopressin, independent of plasma osmolality. Once ethanol is consumed, it is distributed in the blood, brain and muscle tissues. Alcohol is a diuretic that affects five centers in the brain namely the cerebral cortex, limbic system, cerebellum, hypothalamus and pituitary gland and the medulla. The hypothalamus controls the automatic functions of the brain and coordinates endocrine functions through nerve impulse actions on the pituitary gland. Ethanol affects hypothalamus and pituitary gland by increasing urine excretion; inhibiting the pituitary secretion of anti-diuretic hormone (ADH), which makes the kidney reabsorb water. When the ADH levels are decreased, the kidney does not reabsorb water from the urine which

In conclusion, ethanol is a powerful drug that affects several neurological pathways such as the dopaminergic, serotoninergic, γ-amino butyric acid (GABA) and glutamate pathways and causes significant changes in the brain. It also affects the central nervous system and acts to depress brain functions, very much in the style of an anesthetic. Ethanol at low blood concentrations releases behaviors that are otherwise inhibited and usually produces feelings of relaxation and good mood which may facilitate socializing. Thus at low doses, ethanol is possibly useful but caution however needs to be exercised as even low quantities of alcohol affect the ability of the brain (hippocampus) to process information, which in turn impairs memory formation. Higher doses of alcohol affect the brain further by inducing intoxication wherein the person may experience temporary loss of coordination and judgment. Long-term alcohol abuse produces physiological changes in the brain and these changes in the brain chemistry maintain the alcoholic's compulsive inability to cease alcohol consumption being fully aware of the harm caused by alcohol and

results in alcohol withdrawal syndrome upon discontinuation of alcohol.

*Psychology of Health - Biopsychosocial Approach*

part, by protein kinase C (PKC) [33].

and, thus, increased emotional behavior [42].

by which ethanol enhances GABAA inhibitory currents involved a hyperpolarizing shift in the GABAA inhibitory postsynaptic current (IPSC) reversal potential in cortex neurons and increasing the amplitude of GABAA receptor-mediated conductance in septal neurons [31]. When GABAA receptor activation is enhanced

the channel rather than the sustained component of channel opening [32]. The enhancement of the GABAA receptor activation by ethanol may be modulated, in

Glutamate is a major excitatory neurotransmitter in the brain that exerts its effects through several receptor subtypes, including the N-methyl-D-aspartate (NMDA) receptor. Unlike the case with GABA, alcohol inhibits glutamate activity in the brain. In a region of the brain called striatum which contains the nucleus accumbens, ethanol exposure causes a drop in the extra cellular glutamate levels [34]. Following acute administration ethanol, glutamate mediated signal transmission is suppressed in the central nucleus of the amygdala and this effect is enhanced following chronic alcohol exposure [35]. Ethanol inhibits ionotropic glutamate, amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors activity in the brain and N-methyl-D-aspartate (NMDA) receptors are the major target of ethanol's inhibitory action. Ethanol also inhibits the induction of neural plasticity in many brain regions including the dorsal and ventral striatum as a result of inhibitory effects on ionotropic receptors, especially the NMDA receptors

Serotonin is a monoamine neurotransmitter known as 5-HT, a derivative of tryptophan and is extensively found in the gastrointestinal tract, platelets and the CNS. Serotonin plays a role in many brain processes, including regulation of body temperature, sleep, mood, appetite, pain and modulates behavioral response to unfairness [38]. Defect with the serotonin pathway can cause obsessive-compulsive disorder, anxiety disorders and depression. Most of the drugs used to treat depression today work by increasing serotonin levels in the brain [39]. Alcohol increases serotonin release in the nervous system. Increase in concentrations of serotonin in the urine and blood have been observed after taking alcohol. Alcohol exposure alters various aspects of serotonin's synaptic functions and also interferes with the function of serotonin receptors including the 5-HT1A, 5-HT1B, 5-HT2, and 5-HT3 receptors. Each subtype of serotonin receptors has its own specific influence on behavior related to the consumption of alcohol [40]. 5-HT1A may control consummatory behavior, including alcohol consumption while 5-HT1B may contribute not only to alcohol's intoxicating effects, but also influence the development of tolerance to alcohol. 5-HT2 plays a role in alcohol's rewarding effects and contributes to the development of alcohol withdrawal symptoms while 5-HT3 has a part in regulating alcohol consumption. Serotonin also affects other neurotransmitters. For example, alcohol-facilitated serotonin may affect the GABA system [41]. Similarly, alcohol-influenced serotonin works to stimulate increased dopamine production

Dopamine is a neurotransmitter primarily involved in a circuit called the mesolimbic system, which projects from the brain's ventral tegmental area to the nucleus accumbens. It is an excitatory neurotransmitter in the catecholamine family responsible for modulating reward and pleasure. It plays a key role in regulating emotional responses, the reward seeking processes and movement. Several lines of evidence converge to demonstrate that the dopaminergic mesolimbic system plays a significant part in the motivational and reinforcement mechanisms related to behaviors that are vital to survival [43]. Alcohol increases dopaminergic transmission in the mesolimbic pathway and increases the firing rate of dopaminergic neurons, which

enhances the amount of dopamine released in the core of the system.

current through

by ethanol, it may involve enhancement of the initial peak of Cl<sup>−</sup>

**44**

[36, 37].
