Chemical Reactions In Relation To Alcoholism

                                           Chemical Reactions In Relation To Alcoholism


                                                                        Abstract:

Alcohol can be a profound calming agent following a really stressful situation or experience, in the effect that it can help you unwind and be silly and laugh about whatever your problem is. What is tragic is when alcohol becomes a crutch. Once in awhile it is understandable to have a couple drinks, or even for no reason but that a great wine will make some foods taste even better, but to drink to get drunk in excess over and over is how so many people fall down the rabbit hole with little knowledge of how to escape. Once their bodies create that need their bodies to become consumed and even if they do know or remember why they started drinking in the first place they can’t stop because now there is a chemical dependency that they can’t deny without help. C.G. is just one case of many.

        In this paper, I will be discussing the chemical reaction that occurs in a person’s body when alcohol is presented to the body and then abused by the person creating the inability to withdrawal from it. I will be doing this by discussing a case study of a 30-year-old man named C.G.

        C.G. was brought to my attention because of a severe addiction to alcohol that stemmed from a regular excessive consumption of alcoholic beverages. C.G. now experiences tremors that stemmed from alcohol withdrawal seizures and insomnia with bouts of uncontrollable rage, memory impairment, depression, and late-onset diabetes. His constant needs for affiliation with his peers lead to a life that was full of parties and plenty of alcohol at every chance. Now C.G. has trouble buttoning his shirt and is missing several years’ worth of memories, excepting to say that he went to this party or that party and it was “epic”; due to the inhibition of the nervous systems neurotransmitter glutamates reduction effect at the NMDA receptor. C.G. can’t understand normal thought processes without thinking that he isn’t worth anything without a drink in his hand and that’s why he has never been able to keep a relationship together because they always cheated on him, or so he constantly thought. C.G. has to monitor his intake of carbohydrates now for the rest of his life due to his excessive intake of alcohol sugar that has now caused his endocrine system to be disrupted causing inappropriate secretion of insulin and glucagon in his body. C.G. skirts the line of liver fibrosis damage where his liver cells are releasing more and more endotoxins that are causing an excessive build-up of free radicals that his body can’t remove quickly enough and therefore is creating cell damage to the bacterial lining in his gut. I see C.G. weekly to monitor that he is taking his medication of Acamprosate, which is an NMDA receptor antagonist, along with our weekly counseling and a sustained release program of naltrexone, which seems to be working well to control and sustain his cravings for alcohol and alleviate the seizures leaving only controllable mild tremors.

        Beer, a beverage that is produced by the fermentation of yeast was C.G.’s drug of choice, though he wasn’t against mixing in straight shots of liquor, whatever was available, or drinking a bottle of wine, if that was the only thing available. Every time he heard the crack of a can opening or saw the site of a shot being poured his mouth would start to water at how much he anticipated the smooth slide those drinks would take into his body. Like Ivan Pavlov’s salivating dog, C.G. now had a conditioned response to these auditory and visual stimuli. When the alcohol entered his body it went right to work on the brain's reward pathway of the limbic system where dopamine neurotransmitters are released via the ventral tegmental area located near the top of the brain stem. Having an opiate-type feeling of possible pain reduction and/or mood alterations and/or stress relief effects due to the dopamine mechanisms that continual alcohol abuse creates. Since he had been drinking since he was 16, and he was now 30, he had built up a considerable tolerance that allowed C.G. to consume more and more alcohol until he reached his ‘blackout and pass out’ point that would have him wake up, usually somewhere new every time he drank, with no clue as to how he got there.

        Alcohol is made up of ethanol, which is an element made up of a hydroxyl atom that caps one end of 5 hydrogen atoms that are attached to 2 carbon atoms that love to interact with neuro transmitting proteins. Primarily ethanol targets membrane proteins and especially receptors of them and their ion channels where NMDA receptor and GABAa receptor functions of the central nervous system are inhibited by intoxicating amounts. The actual ethanol reaction is as follow:

“Following the release of dopamine (DA) induced by ethanol, the DA D1 receptor is stimulated. Subsequently, the activity of adenylyl cyclase (AC), through coupling to stimulatory G proteins (Gas), results in an increase in cAMP concentration and in the activation of cAMP-dependent protein kinase A (PKA) signaling. cAMP induces this activation by promoting the disassociation of the regulatory subunit (R) of PKA from the catalytic subunit (PKA-Ca). PKA-Ca then leads to phosphorylation of the transcription factor cAMP response element-binding protein (CREB). Exposure to ethanol also influences the expression of Ca2=/calmdulin-dependent protein kinase IV (CaMKIV)and thereby CREB phosphorylation in the NAC. These events finally result in altered transcription of genes containing a cAMP response element (CRE) in their promoter regions such as corticotrophin-releasing hormone (CHR), neuropeptide Y (NPY), prodynorphin (PDYN), and brain-derived neurotrophic factor (BDNF). Not only is CREB phosphorylated upon activation of D1 cAMP-PKA signaling but also DARPP-32, which is a 32-kDa protein that is expressed predominantly in striatal medium spiny neurons. In its phosphorylated form, it acts as a potent inhibitor of protein phosphatase 1 (PP1). The function of PP1 is the dephosphorylation of the NR1 subunit of the NMDA receptor. Therefore, PP1 inhibition by DARPP-32 leads to augmented NMDA receptor phosphorylation, which then increases channel function and counteracts the acute inhibitory action of ethanol on this receptor. Deletion of pharmacological blockade of G proteins (Gas), By, PKA or DARPP-32 leads to alterations in alcohol (ETOH)…” (Rainer Spanagel, 664)

“The effects of alcohol on the body’s neurochemistry are more difficult to examine than some other drugs. This is because the chemical nature of the substance makes it easy to penetrate into the brain, and it also influences the phospholipid bilayer of neurons. This allows alcohol to have a widespread impact on many normal cell functions and modifies the actions of several neurotransmitter systems.” (Wikipedia, Alcoholism)

        So because C.G. is a male he is twice as likely as a woman to form a chemical addiction to alcohol. Which in terms of addiction, it is not the consumption that makes you chemically addicted but the withdrawal. The more heavily and frequently C.G. consumed alcohol it became increasingly harder to abstain from drinking. At one point he could go several days, even a week or so without drinking, but as time progressed his body tolerance went up and so did his craving so that if he did try to abstain he physically couldn’t. His brains receptors became desensitized and were getting eliminated, which allowed for uncontrollable synapses firing that created his anxiety that elevated his heart rate up that produced deliriums that his girlfriends were fraternizing with other men that produced uncontrollable rage outbursts that brought on the tremors and shakes that eventually turned into seizures anytime he tried to prove that he wasn’t an alcoholic.




                                                                          Works Cited:

• Alcoholism, Wikipedia http://en.wikipedia.org/wiki/Alcoholism
• Alcoholism: A Systems Approach From Molecular Physiology to Addictive Behavior: Spanagel, Rainer: Physiological Reviews Volume 89 Issue 2 Pages 649-705 DOI: 10.1152/Physrev-00013.2008 Apr. 2009
• Physiology of Behavior: Neil R. Carlson: Eleventh Edition pages 631-633; 640-641

Memory Formation

                Memory Formation

        Memory formation occurs when we learn something new. With every new piece of information we learn we alter our nervous system, therefore discovering a new way to think, perform, plan, and perceive. Thus allowing us to gain a new memory of something we have learned that has impacted our lives enough to change our existing thought processes.

        This all starts with a perception of a current situation. From the point in which the situation is introduced to our visual association cortex, auditory association cortex, and somatosensory cortex it starts its’ incredibly fast way to our hippocampal area, where it enters via the entorhinal cortex, where all of the information collected gets compressed into one situation or experience. The hippocampus also determines where this situation or experience will get encoded to, whether it is a long term memory or a short term memory. Also, even though the situation/experience has been compressed, the hippocampus decompresses it to store each piece of this new information from this experience in its appropriate place. This is done through neural transmissions that are made by various electro energies and chemicals that make up our bodies.

        Neural transmission is the process by which dendrites of a neuron become active sending a signal to the soma that then gets carried through the axon by way of an action potential that travels through the axon that is covered beaded necklace style in the myelin sheath, to the terminal buttons which releases a neurotransmitter. In between the myelin sheathed parts of the axons are nodes of Ranvier. These little openings allow for the regeneration of an action potential by allowing for polarization or depolarization of ions to occur in these sections. There are numerous neurons in the body that speak to each other in chain-link fashion by way of synaptic transmission via synaptic clefts and vesicles, that are located on the terminal buttons that are attaching to dendrites. These can attach to smooth dendrites or to a dendrite spine. Neurotransmissions are released via presynaptic membranes that are located adjacent to the terminal buttons and received by postsynaptic membranes located opposite of the terminal buttons. These synapses communicate by way of staring each other down at the end of the terminal button, where the neurotransmitter is eventually diffused. Before it’s diffused it was able to open ion channels to allow proteins such as calcium, chloride, potassium, and sodium, to enter and exit by way of direct and indirect fashions that can cause excitatory or inhibitory postsynaptic potentials which can cause neural integration. The action potential starts the process of neurotransmission by waiting till a bunch of synapses are "docked" (as described on page 54 of our textbook Physiology of Behavior by Neil R. Carlson) at a presynaptic membrane where proteins get together with other proteins. After that has happened calcium ion channels help diffuse the neurotransmitter. All of these transmissions, synapses, and potentials are occurring and/or traveling through our central and peripheral nervous systems collecting and distributing information.

        The neurons of our situation/ experience then become a long term potentiation by traveling the axons of the entorhinal cortex where the hippocampus’s formation of synapses with the granule cells takes shape via electrical stimulation. This electrical stimulation comes via the perforant path and ends up the population of excitatory postsynaptic potentials which determine the strength of the synaptic connection (as I have listed in my notes that I took from my understanding from page 439 of Physiology of Behavior by Neil R. Carlson). The strength of the synaptic connection is an indication of how strongly the memory will be encoded or not thus also determining its final destination in our short or long term memories and what subsets each portion of that memory will find itself in. For instance, you may remember a certain characteristic about a situation or experience more than the whole of the experience so the strength of that portion of the synaptic connection will fire stronger allowing the long term potentiation to occur, than that of a characteristic you did not pay much attention to and let fade to the background thus an LTP will not occur. In order for an LTP to occur, it must have activation of synapses and depolarization of postsynaptic neurons. Once that is achieved basic memory formation has occurred.

        Subsequently, seizures can occur if there is a biochemical abnormality in the human body GABA secreting neurons that inhibit large numbers of GABA to be secreted causing epileptic seizures to occur. Such was the case when Henry Molaison had to have his hippocampus and entorhinal cortex removed due to continuous seizures that impaired his life dramatically after a bicycle accident he had at age 7. He then had both of those sections of his brain removed in an effort to stop the seizures. The surgery was a success however he permanently lost the ability to form new memories. He was, however, able to learn new motor skills but never attach those motor skills to an event in which he learned them; which is sad for H.M. since learning through our experiences by attaching our learned information to a perceptual time and place when we learned it, allows us to achieve greater learning ability. It was an asset to the neurobiology field since it shed considerable light on how important the hippocampus is to the establishment and organization of our memories, which is infinitely important to our depth of knowledge.