**2. Alcohol and the brain**

#### **2.1. How does alcohol act at the neurological level?**

Brain chemistry is affected by alcohol through alteration of neurotransmitters. Neurotransmitters are chemical messengers that send out the signals all through the body and control thought processes, behavior and sensation processes. Neurotransmitters are either excitatory (excite brain electrical motion) or inhibitory (decrease brain electrical motion). Alcohol increases the effects of the inhibitory neurotransmitter GABA in the brain. GABA causes the lethargic movements and garbled speech that often occur in alcoholics. At the same time, alcohol inhibits the excitatory neurotransmitter glutamate, which results in a suppression of a similar type of physiological slowdown. In addition, alcohol also increases the amount of chemical dopamine in the brain center, which creates the feeling of pleasure after drinking alcohol. Just after a few drinks, the physical effects of alcohol become perceptible. These effects are linked to blood alcohol concentration (BAC) (**Table 1**). The level of BAC rises when the body takes up alcohol faster than it can release it.

In the brain, various centers have been affected due to alcohol, both upper and lower order. As the BAC increases, more centers of the brain are affected (**Figure 1**) [3]. The order in which brain centers are affected by alcohol consumption is as follows:


When people consume alcohol, about 20% is absorbed in the stomach and almost 80% is

**b.** heavy meal consumption before drinking. An empty stomach will fasten the alcohol

Absorbed alcohol enters the blood stream and is carried all through the body. Upon reaching the body, simultaneously the body works to eliminate it. The 10% of alcohol is removed by the kidneys (urine) and lungs (breath). Left-out alcohol is oxidized by the liver, converting

Alcohol is absorbed in the stomach and intestines through the blood stream and crosses the blood-brain barrier (BBB) after consumption. Alcohol is metabolized through the mitochondrial cytochrome P450 (CYP2E1) and catalase in the liver or the brain. In the brain, alcohol metabolism by CYP2E1 produces acetaldehyde and alcohol is considered to be the only source of acetaldehyde. The rest of the acetaldehyde may go through the brain by an enzyme called alcohol dehydrogenase (ADH) which is found in the liver and helps in conversion of alcohol to acetaldehyde. Target of alcohol is considered to be ADH. Alcohol binds through its hydroxyl (─OH) group and zinc atom on ADH [1]. Disulfiram (antabuse), one of the first approved treatments for alcoholism, showed its mechanism by inhibiting the ADH enzyme. When taken regularly, disulfiram decreases the drinking capacity because of the aversive effects [2].

Brain chemistry is affected by alcohol through alteration of neurotransmitters. Neurotransmitters are chemical messengers that send out the signals all through the body and control thought processes, behavior and sensation processes. Neurotransmitters are either excitatory (excite brain electrical motion) or inhibitory (decrease brain electrical motion). Alcohol increases the effects of the inhibitory neurotransmitter GABA in the brain. GABA causes the lethargic movements and garbled speech that often occur in alcoholics. At the same time, alcohol inhibits the excitatory neurotransmitter glutamate, which results in a suppression of a similar type of physiological slowdown. In addition, alcohol also increases the amount of chemical dopamine in the brain center, which creates the feeling of pleasure after drinking alcohol. Just after a few drinks, the physical effects of alcohol become perceptible. These effects are linked to blood alcohol concentration (BAC) (**Table 1**). The level of BAC rises when

In the brain, various centers have been affected due to alcohol, both upper and lower order. As the BAC increases, more centers of the brain are affected (**Figure 1**) [3]. The order in which

absorbed in the small intestine. Alcohol absorption is related to the two main factors:

alcohol into acetaldehyde first and then further converted to acetic acid.

**a.** concentration of alcohol and

**1.2. Alcohol metabolism and distribution**

**2. Alcohol and the brain**

**2.1. How does alcohol act at the neurological level?**

the body takes up alcohol faster than it can release it.

brain centers are affected by alcohol consumption is as follows:

absorption.

14 Drug Addiction


#### *2.1.1. Long-term effect of alcohol on the brain*

Continuous or excessive drinking can lead to undeviating injury, causing the brain to shrivel. This leads to deficiency in fibers that transfers the information between neuronal cells. Excessive alcohol leads to a condition called **Wernicke-Korsakoff syndrome** (deficiency of thiamine) [4]. Alcohol interference leads to this deficiency, as it blocks the way of vitamin B absorption in the body. Symptoms of the Wernicke-Korsakoff syndrome are mental perplexity, lack of fine movements, memory and learning problems.


**Table 1.** The effect of alcohol exposure on the brain.

**1.** In-vivo studies yielded a result showing antioxidant therapy and vitamin E which is used

Effect of Alcohol on Brain Development http://dx.doi.org/10.5772/intechopen.73693 17

**2.** Treatment with l-octanol (paradoxically an alcohol itself) on developing mouse embryos

**3.** NAP and SAL have the same property as octanol. They both help in protecting nerve cells

**4.** A compound called MK–801 that blocks glutamate that helps with alcohol withdrawal [10].

Glutamate receptors include metabotropic glutamate receptor (mGlu), *N*-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Glutamate exhibits its action on binding to these receptors, resulting in the activation of G-proteins which further leads to amplification of phospholipase C, diacylglycerol (IP3DAG)

During alcohol drinking, there is a release of excessive glutamate leading to neuronal cell

**1.** Activation of glutamate receptors causes toxicity [12], resulting into Ca+2 ion influx, Na+ influx, nitric oxide (NO) generation and depolarization of mitochondria. This will lead to untenable elevations in ATP, mitochondrial collapse, dendritic beading and depolymeriza-

A study has been carried out on 13 abstinent young alcoholics showing a major increase in glutamate to creatine ratio by proton magnetic resonance spectroscopy and magnetic resonance imaging [15]. Furthermore, an alteration in glutamate is linked to altered short memory loss. Immediate administration of alcohol (acute dose) prior to the microdialysis experiment would end up into an increased glutamate release. Earlier studies showed that administration of either 2 or 3 g/kg ethanol to immature rats elicits a decrease or no modification in the release of glutamate into the N-acetyl cysteine (NAC) [16]. Researchers showed that there is a genetic component that probably contributes to the brain injury occurring in "binge drinking" alcoholics [17]. In binge drinking, alcohol models, there are no reports of increased NMDA receptors [18]. In one study, "binge- drinking" individuals with compensated alcoholic cirrhosis, dosing 80 g of ethanol, showed a transient increase in serum nitrates and nitrite resulting in an increase in NO production in certain tissues (liver and brain) [19]. During the period of chronic alcohol toxicity, basal concentration of glutamate seems to be normal in various

During chronic alcohol consumption, NMDA receptor (NMDAR1 and NMDAR2B) levels seem to be increasing in numbers and decreasing in sensitivity [21] in the nucleus [22], the

significantly reduced the rigorousness of alcohol's effects [8].

**2.2. Alcohol-induced neurotransmitters and its effect on the neurons**

regions of the brain though blood alcohol levels are high as 2 g/l [20].

for treating FAS.

*2.2.1. Glutamate*

against a variety of toxins [9].

and calcium-dependent protein kinases [11].

death. This occurs through two pathways:

tion of microtubule [13].

**2.** Oxidative toxicity to glutamate [14].

striatum [23] and the hippocampus [20].

**Figure 1.** Effect of alcohol on various brain centers.

Heavy or continuous consumption of alcohol can lead to the liver injury. The liver is the chief organ responsible for converting alcohol into nontoxic byproducts and taking them out of the body. Excessive alcohol consumption leads to prolonged liver dysfunction which may also harm the brain, leading to a severe fatal brain disorder known as **hepatic encephalopathy** [5]. Studies have confirmed that at least two toxic substances, **ammonia and manganese,** play an important role in the progress of hepatic encephalopathy.

**Treatment—**Strategies that have been used to treat or prevent the development of hepatic encephalopathy are as follows:


#### *2.1.2. Alcohol and the developing brain*

Alcohol consumption during pregnancy can lead to changes in the physical, learning and behavioral effects in the developing brain and it is known as **fetal alcohol syndrome (FAS)** [8].The brains of these people may have less size (i.e., microencephaly) and also a small amount of brain cells (i.e., neurons) that function accurately resulting in long-lasting problems in learning and behavior.

**Treatment:** Researchers are looking forward to treat or prevent brain damage, such as associated with FAS.

