The brain has many receptors, and each has its own “key” to either turn it on or off.
The brain has many receptors, and each has its own “key” to either turn it on or off.
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Assignment Details: The brain has many receptors, and each has its own “key” to either turn it on or off. An agonist is something that binds to the receptor site to produce a wanted reaction, or biological response. An example would be to give a patient a stimulant to increase alertness and focus. The stimulant is an agonist for dopamine and norepinephrine. When stimulated, the person is more able to focus and should have more concentration overall. Conversely, an antagonist does the opposite. The antagonist is given to stop a biological response from happening by limiting the amount of a neurotransmitter available for uptake in the synapses. An example of this is naltrexone which is given to block opioid receptors. When the receptors are blocked, the person does not feel the biological response they would normally get from the opioid, making it less desirable. It is primarily given for those experiencing opioid addiction. There are two types of receptors within the transmission chain, the ion-gated and the g-protein-coupled receptors (Libretexts, 2022).
There are receptors that require certain neurotransmitters to activate them, these are called ion-gated channels. The other type is the g-protein-coupled receptors, which are those that respond to and are activated by several neurotransmitters, not just one. The two types are similar in that both are able to activate multiple neurons simultaneously, thus speeding up transmission of information. When we give pharmaceuticals that are designed to impact the brain, what we are ultimately trying to accomplish is a change in our patient’s behavior. This study of this change is referred to as epigenetics (Libretexts, 2022).
Individuals are born with pathways in which their DNA and genes express themselves, the traits that are inherited in other words. Epigenome refers to the way in which these traits are expressed. The epigenome is inherited and therefore established during fetal development; however, we can change those pathways later in life with psychotropic medications. The medications bind with the receptors and cause behaviors to divert from the inherited pathways already established in the brain (Toth, 2021). Because individuals are born with different innate pathways in their brains, this also means that according to those pathways, the same medication may have very different effects from one person to the other. This can be known as an idiosyncratic drug reaction, which is a reaction to a medication that is unusual and unpredictable, specific to a particular person. As a practitioner, we must be aware of this possibility when prescribing. Many psychotropic medications are started low and increased gradually to assure there are no negative effects.
ASSIGNMENT- (SHORT ANSWERS OR HALF A PAGE WITH 2 REFERENCES). Does the above explanation influence your understanding of these concepts, be sure to share how and why. Include additional insights you gained
If you think these concepts might have been misunderstood, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective*
2ND HALF OF THE PAGE
ASSIGNMENT- (SHORT ANSWERS OR HALF A PAGE WITH 2 REFERENCES). Does the above explanation influence your understanding of these concepts, be sure to share how and why. Include additional insights you gained
If you think these concepts might have been misunderstood, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective*
Agonist-to-Antagonist Spectrum
Full agonists, partial agonists, inverse agonists, and antagonists fall on the agonist-to-antagonist spectrum in terms of effects on neurotransmitter receptors. On the one end, full agonists cause the receptor to induce maximum signal transduction and on the other end, inverse agonists prevent any signal transduction. Partial agonists cause an intermediate increase in signal transduction and are each set at a certain level. Antagonists fill the receptor to “reset” the signal transduction to the natural neutral point with only constitutive activity, so they may act to either increase or decrease the signal transduction depending on if the receptor had been filled by an agonist or inverse agonist.GCPRs vs. Ion gated channels
G-coupled protein receptors are slower acting than ion gated channels. An example of GCPRs is the muscarinic acetylcholine receptor. When the receptor is activated, Gq/11 proteins allow phosphoinositides to produce inositol 1, 4, 5-triphosphate (IP3) and 1, 2-diacylglycerol (DAG), increasing intracellular calcium levels and protein kinase C (PKC) activity, with the end result being adenylyl cyclase suppression and the cAMP inhibition (Ruan et al., 2021). Evidently, GPCR activation leads to a cascade of cellular responses with downstream effects.
Ion gated channels are rapid acting and can cause synaptic transmission in milliseconds (Alexander et al., 2021). When a neurotransmitter binds to an ion gated channel receptor, there is an immediate reaction: depolarization, which allows ions to flow through and induce further chemical reactions. Nicotinic acetylcholine receptors, nAChRs, are an example of ion gated channel receptors. NAChRs are associated with sodium, potassium, and calcium ions and are found in both the CNS and PNS. NAChRs are clinically significant as they are involved in nicotine addiction, nicotine-induced behaviors, small-cell lung carcinomas, Alzheimer’s disease, schizophrenia, Parkinson’s disease, depression, myasthenia gravis, and neuropathic pain (Ho et al., 2020).
Epigenetics
Epigenetics is the study of genes turning on or off by heritable and reversible changes in structure, but not sequence, in reaction to life experience. DNA modification, histone modification, chromatin remodeling, and RNA regulation through miRNAs are examples of structural changes that can occur with epigenetic processes. Epigenetics has clinical application in psychiatry, as many psychiatric illnesses develop as a result of not only genetic predisposition, but also life experience that affects genetic expression. Treating major depressive disorder with pharmacotherapy is difficult because of the variability of patient response to medications. Epigenetic studies examining levels of miRNA amongst responders and non-responders to SSRIs have demonstrated that individuals with low levels of miR-1202 are likely to respond to SSRI treatment (Kuehner et al., 2019). Thus, epigenetic testing can provide support for efficient and cost-effective personalized pharmacotherapy for MDD.Clinical Application
In the clinical setting it is important to understand medications’ mechanism of action to provide safe, effective and individualized care. For example, treating a patient with bipolar disorder, anxiety, and renal impairment would be require thoughtful medication planning due to potential contraindications. First, it would be important to note that SSRIs are contraindicated for bipolar disorder due to the risk of induced mania, although SSRIs are first-line treatment for anxiety disorder (Strawn et al., 2018). In addition, lithium, the first-line medication for bipolar disorder is contraindicated for renal impairment. It would be important to understand the mechanism of action of SSRIs in reducing anxiety and lithium in stabilizing mood in bipolar disorder to choose alternative medications with similar effects but minimal adverse effects and contraindications for this individual.Epigenetics is also important to understand as a provider with prescriptive authority. As mentioned above, epigenetic testing is allowing prescribers to individualize treatment for MDD. In addition to miRNA testing, hypermethylation at specific CpG-sites has been associated with antidepressant treatment response (Engelmann et al., 2022). By performing epigenetic testing for levels of miRNA, miR-1202, and hypermethylation at cg02107110, the provider has a greater chance of choosing an effective medication and avoiding ineffective medications for the patient. For example, before beginning SSRI therapy for a patient with MDD, it would be beneficial to perform the epigenetic testing mentioned previously to avoid unnecessary cost and disappointment with unresponsiveness to treatment if the patient tests as a likely non-responder.
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