Year 11 Biology

FA3 Research Investigation

Hayley Westman

Due Date: 29/08/23

Teacher: Miss TAYLOR

Table of Contents
Impacts of extended cocaine abuse on homeostasis through neurotransmitter dysregulation......................2
Claim: The implications of extended illicit drug use on the body is irreversible.................................................2
Rationale............................................................................................................................................................2
Research Question:.............................................................................................................................................3
Analysis + interpretation:...................................................................................................................................3
Evidence 1:.........................................................................................................................................................3
Evidence 2:.........................................................................................................................................................4
Conclusion and Evaluation..................................................................................................................................5
Quality of evidence.........................................................................................................................................5
Conclusion to claim and research question....................................................................................................5
Evaluation.......................................................................................................................................................6
Reference:..........................................................................................................................................................7

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 Impacts of extended cocaine abuse on homeostasis through neurotransmitter dysregulation

Claim: The implications of extended illicit drug use on the body is irreversible.
Rationale
Extended illicit drug abuse is a common problem occurring worldwide often impacting significantly on the body with
many permanent and irreversible effects. (DrugFacts Understanding Drug Use and Addiction DrugFacts, 2018)
Throughout this research task the claim “the implications of extended illicit drug use on the body is irreversible” will be
explored, though due to its broadness, this research will focus specifically on cocaine’s effects on homeostasis through
neurotransmitter dysregulation. It was due to the extended research and sufficient sources discovered on the
dysregulation of the neurotransmitter’s dopamine, and serotonin in response to cocaine, this claim was further
narrowed down.

Homeostasis is the maintenance of a constant internal environment, imperative for all biological processes to occur in
the body and is mediated by feedback systems. This means through feedback loops the body must recognise and
respond to internal and external stimuli to maintain this state of equilibrium which is often referred to as the stimulus-
response model. Hormones and neurotransmitters control many cell activities and are key in maintaining homeostasis.
Neurotransmitter regulation is too controlled by feedback mechanisms often involving negative feedback loops. (Hiller-
Sturmhöfel and Bartke, 1998) After neurotransmission has occurred, they are then reabsorbed by the nerve cells which
is known as reuptake. However, if reuptake fails to occur homeostasis is at risk of being disturbed, this is known as
neurotransmitter dysregulation. It is through the consequences on homeostasis from neurotransmitter dysregulation,
the impact of extended cocaine abuse will be examined in this report.

“Substance abuse refers to excessive use of a drug in a way that is detrimental to self, society, or both.”(Birrer, O’connor
and Kane, 2016, Chapter 206) This research investigation will focus on the substance abuse of cocaine, a powerful illicit
stimulant drug that in some form has been used and abused for thousands of years. (National Institute on Drug Abuse,
2016) When an illicit substance such as cocaine is absorbed, it blocks the reuptake of neurotransmitters and hormones,
in particular dopamine and serotonin, pushing more into the network where they boost energy and promote feelings of
euphoria. It is this neurotransmitter dysregulation that allows the drug to be incredibly addictive. Dopamine and
serotonin regulation in the body are the primary aspects of homeostasis being investigated in response to substance
abuse particularly of cocaine.

Dopamine is a type of neurotransmitter found in the brain, essential for the reward pathway and promoting feelings of
pleasure, satisfaction and motivation (Juárez Olguín et al., 2016). “In a normal communication process, dopamine is
released by a neuron into the synapse where it binds to specialized proteins called dopamine receptors on the
neighbouring neuron” (National Institute on Drug Abuse, 2016). It is in this process that dopamine acts as a chemical
messenger to then subsequently be reabsorbed by a different specialised protein after neurotransmission has occurred.
However, cocaine is known to impend this process (National Institute on Drug Abuse, 2016b).

Serotonin is a “neurotransmitter that modulates neural activity and a wide range of neuropsychological processes.”
(Berger, Gray and Roth, 2009) It controls your mood and is responsible for feelings of happiness. When nerve cells in the
brain send signals to one another, a release of neurotransmitters including the chemical serotonin occurs. The
neurotransmitter is then reabsorbed before more can be released, however, drugs such as antidepressants or cocaine
can interfere with this process. (Salters, 2023)

To ensure specificity and precision of this research the key terms and concepts ‘repeated cocaine use’, ‘homeostasis’
and ‘neurotransmitter dysregulation’ have been appended to develop a specific and relevant research question for this
investigation. Ultimately, “To what extent does reoccurring cocaine abuse impact homeostasis in the body through
neurotransmitter dysregulation” was derived from the claim.

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Research Question:
“To what extent does reoccurring cocaine abuse impact homeostasis in the body through neurotransmitter
dysregulation?”

Analysis + interpretation:
This research investigation will analyse two studies to determine the extent, reoccurring cocaine abuse impacts
neurotransmitter regulation and homeostasis. An arrangement of the most appropriate studies found have been
compiled and analysed throughout this investigation to answer the research question. The following studies were
determined to be the most relevant:

1. Rougé-Pont et al. (2002) published in the Journal of Neuroscience aimed to Research the contribution of the
DA D2 (dopamine type 2) receptor in control of the increase in extracellular dopamine concentration in
response to illicit drugs.
2. Yuen et al. (2022) published in the Journal of Neurophysiology investigated the acute effect of the
psychostimulant cocaine on electrical stimulation-evoked serotonin release in male rats using N-shaped fast-
scan cyclic voltammetry (N-FSCV).

Evidence 1:
This study titled “Changes in Extracellular Dopamine Induced by Morphine and Cocaine: Crucial Control by D2
Receptors” measured the extracellular dopamine levels in the striatum of mice lacking D2R expression (D2R-/-). This
was done after the administration of the psychostimulant cocaine and the opioid morphine using the in vivo
microdialysis technique. (Rougé-Pont et al., 2002)

Figure 1 illustrates the induced change in the extracellular concentration of dopamine in wild-type (WT) and D2R-/-
mice. The relationship between cocaine and increased dopamine is highlighted in Figure 1 when comparing the effects
of the drug to the placebo (saline solution). As seen on the graph after 0 minutes (the point of administration of
cocaine) there is an immediate surge in dopamine in the mice that consumed 20mg/kg and 40mg/kg of cocaine
compared to those that consumed the placebo which was ineffectual. This trend assists in answering the research
question as it highlights the effect cocaine had on homeostasis through significant increase in dopamine concentration.
While the significant trend of increased dopamine due to cocaine ingestion is clear, the eventual reuptake of the
neurotransmitter after the drug has reached its half-life (Burnett et al., 2023) is also illustrated following approximately
40 minutes of consumption. Each concentration for both WT and D2R-/- mice can be observed to follow both trends
stated relatively consistently. The final relevant trend displayed on the graph is the effect the higher concentration of
cocaine had on dopamine concentration. It is noticeably shown that the 40mg/kg dose, produced a far greater
concentration of dopamine in comparison to the lower dose.

Despite the usefulness of this piece of evidence, a limitation arose regarding the age of the study as it was published in
2002. This limitation affects validity as the argument of the data being outdated is feasible (over 20 years since
publication) which suggests the accuracy of the results is possibly jeopardised. “There is consensus among scientists and
researchers that articles less than five years old are recent publications.” (next Gen. referencing, 2022) A further
limitation was the relevance of the rest of the study. While this graph was useful majority of the remaining information
from the study was not relevant or too complex to be used and interpreted for this research investigation which
hindered the overall usefulness of the source.

Regardless, the significant trends presented in figure 1 indicates the distinct relationship between the variables in the
research question, highlighting the effect cocaine has on increased extracellular dopamine levels. This relationship
follows consistent with literature including the national institute on drug abuse which states “cocaine acts by binding to

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the dopamine transporter, blocking the removal of dopamine from the synapse.” (National Institute on Drug Abuse,
2016) From this evidence when considering the research question, it can be concluded the considerable
neurotransmitter dysregulation produced by cocaine would greatly affect homeostasis even at concentrations as low as
20mg/kg directly after administration.

Figure 1 (Rougé-Pont et al., 2002)

Evidence 2:
In 2022 the study “Cocaine increases stimulation-evoked serotonin efflux in the nucleus accumbens” was published by
the Journal of Neurophysiology and it was through animal studies that serotonin’s role in addiction was explored. (Yuen
et al., 2022)

In a detailed examination of Figure 2 the following relevant trends can be recognised to answer the research question
regarding to cocaine’s impact on homeostasis. The release of stimulation evoked serotonin increased significantly after
5 minutes from the time of cocaine injection. This increase is further highlighted on the graph when comparing
cocaine’s effects to the baseline or saline injection (placebo), which both are ineffectual in increasing serotonin release.
This noteworthy trend aids to answer the research question as it is highlights cocaine’s significant impact on
homeostasis through increased serotonin. However, the results in Figure 2 also show the rapid decrease in stimulation-
evoked serotonin release after the initial ‘high’ fades which is shown after approximately 10 minutes. This trend of
decreasing serotonin release continues over the remainder of the results, eventually leading the measured stimulation-
evoked serotonin release to fall below the baseline approximately 40 minutes following the injection of cocaine. This
decrease in serotonin release corroborates with literature discussing the effects of the ‘comedown’ from a variety of
drugs including cocaine on homeostasis. “A drug comedown occurs as the effects of a drug wear off. Users describe the
feeling as coming down because it happens as the high feeling from the drug dissipates. (Brown and Coy, 2021)

Predominantly this study was notably valuable with few limitations and a high standard of validity however occasional
limitations arose. The complexity of this study was the first limitation faced however with further understanding and
explanation this limitation would likely become a strength for this source. The other limitation confronted was that this
study was an animal experiment. It is often reasoned animal research, particularly that relating to pharmaceuticals and
environmental agents, may be a poor predictor of human experience. (Bracken, 2009) To oppose this limitation
supporting sources could be used in conjunction with the evidence presented from the study to ensure the reliability
and validity of the results is consistent.

This study and the significant trends displayed in the evidence contribute to answering the research question through
the demonstration of dysregulation of the neurotransmitter serotonin caused by cocaine. The trends displayed are
supported by many sources including a review where Assistant Professor Loren Parsons is quoted to say, "When
ethanol, cannabinoids, opioids, or psychostimulants are taken into the body, serotonin levels in the brain are elevated.”

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Markedly, he further adds, “this elevation in serotonin plays a role in the motivation to continue taking drugs.” (Bardi,
2023) From this evidence when considering the research question, it can be concluded while dopamine is a key
neurotransmitter significantly affecting homeostasis when influenced by cocaine, the drug’s adverse effects also extend
to impacting homeostasis through neurotransmitter dysregulation of serotonin.

Figure 2 (Yuen et al., 2022b)

Conclusion and Evaluation

Quality of evidence
Two primary pieces of evidence (figure 1 and figure 2) were utilised in combination with a variety of other sources and
quotes from admirable studies and systematic reviews. The research throughout this report aimed to determine the
extent repeated cocaine abuse impacts homeostasis in the body through neurotransmitter dysregulation, particularly
focusing on the neurotransmitter’s dopamine and serotonin. Over the course of this report the reliability and validity of
the sources utilised were key aspects considered when source selection occurred along with relevance and contribution
to answering the research question. Evidence with qualities that suited this target were difficult to acquire due to the
desired standard of sources and the specific nature of the research question, regardless, a collection of useful and
credible sources was achieved. Nonetheless, limitations still arose. The time since publication of the first study was the
primary limitation of the piece of evidence as it could be argued to be outdated and impact on the validity of the
information and results presented. Data primarily collected from animal studies was a major flaw when evaluating the
second evidence. Animal studies possibly being a poor predictor of human experience is often argued in animal-based
research. As stated earlier this is likely due to the validity of the research and information for human outcomes
presented being in question. Regardless, the sources used over the course of the investigation were of a high standard
and useful in answering the research question.

Conclusion to claim and research question

The aim of this investigation was to answer the following research question: “To what extent does reoccurring cocaine
abuse impact homeostasis in the body through neurotransmitter dysregulation?” The evidence from Rougé-Pont et. al,
(2002) highlighted the considerable neurotransmitter dysregulation produced by cocaine which greatly affects
homeostasis directly after administration. Additionally, Yuen et. al (2022) determined the significant influence cocaine
has by impacting homeostasis through neurotransmitter dysregulation of serotonin. The weight of the evidence

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presented throughout the investigation in combination with literature and background information suggests the effect
cocaine has on neurotransmitter regulation is not only evident but significant and greatly affects homeostasis. This
conclusion produced from the evidence analysed throughout the report positively supports the claim.

Evaluation
Throughout this research investigation, the opportunity for many improvements and extensions occurred to further the
investigation and combat the limitations encountered. Extended detailed understanding of current evidence and the
collection of a variety of newer more recent sources is a recommended improvement for this report. Additional
research into other illicit substances, hormones, different neurotransmitters and human studies would be valuable
extensions to the investigation. It is notable to mention however, that as a result of morality and legal reasons the
ability for data from human studies is limited. Despite these improvements and extensions, consideration of many
other studies with both alternative and supporting evidence, different methodologies and peer reviews would be
demanded for a truly effective and definitive answer.

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Reference:
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