Clinical Features of Amphetamine Intoxication and Dopamine Hypothesis of Schizophrenia

This article discusses the clinical features of amphetamine intoxication, how amphetamines act on the CNS, dopamine hypothesis of schizophrenia, other neurotransmitters associated with schizophrenia, auditory hallucination manifestation and areas of the brain involved, and medications to alleviate symptoms. It also includes side effects of antipsychotics, benzodiazepines, and tiapride.

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Question 1
Clinical features of Amphetamine intoxication
Amphetamine intoxication can present clinically through several ways which may include both
mental and physical symptoms and changes in behaviors (Ciccarone, 2011). This may include;
I. Auditory, visual and tactile hallucinations. This is where an individual perceive sounds,
vision and touch respectively in absence of a stimuli.
II. Paranoia, which may show up through an individual having delusions of persecutions or a
person see himself or herself to be of much important even when not. A person may also
have anxiety (Cunha-Oliveira, Rego, Carvalho, & Oliveira, 2013). Which is having the
fear of the unknown.
III. Increase in heart rate and blood pressure may also be noticed
IV. Loss of weight and reduced appetite. One also develop upset in digestion.
V. Insomnia. Where a person experience difficulty in falling asleep.
VI. Mood swings and aggressive behavior. The mood of a person just changes abruptly.
VII. Loss of interest in activities that one has been doing and isolation.
According to National Institute on Drug Abuse, when methamphetamine, a derivative of
amphetamine is the drug being abused, then one may experience skin sores, dental problems and
severe loss of weight (National Institutes of Health, 2011).
How amphetamines act on CNS

Amphetamines act on the central Nervous system by stimulating it to produce extra brain
activity, enhancing sense of well-being and increasing the alertness (Gardenhire, 2015).
Amphetamines does that by acting particularly on three neurotransmitters; dopamine, serotonin
and noradrenaline (Brensilver, Heinzerling, & Shoptaw, 2013). It increases the levels of this
neurotransmitters. Neurotransmitters can be described as chemical substances which allow
information to reach the receptor site by conducting signals between neurons and nerve cells.
Dopamine is a neurotransmitter which is responsible for reward, pleasure, attention and
movement. Amphetamines act on this neurotransmitter more than the rest. Serotonin influences
appetite, anger and mood. It also disturbs body functions such as, sleep pattern, blood pressure
and temperature. Noradrenaline deals with the body’s fight or flight mechanism and therefore
aids in production of adrenaline which gives the body its sudden energy and alertness. When
amphetamines are therefore taken, all the three neurotransmitters are released to the brain. This
creates a euphoric feeling to the person. The person gets an intense feeling of excitement and
alertness.
Question 2
a. Dopamine hypothesis of schizophrenia
The dopamine hypothesis of schizophrenia is a model which tries to prove that the symptoms
may be as a result of dopamine being excess in the mid-brain and less in the prefrontal cortex.
This hypothesis originated from the discoveries that those drugs which block dopamine, that is
dopamine antagonists, lowers the positive symptoms of schizophrenia (Kendler, & Schaffner,
2011). An example of dopamine antagonist is antipsychotics. Moreover, the drugs which

increases dopamine, for example, L-DOPA, can at times consist the side effects of developing
psychosis-like symptoms. This drugs are those which are used to cure Parkinson’s disease.
b. Other Neurotransmitters associated with schizophrenia
Serotonin- some theories have proven that serotonin contributes to the symptoms of
schizophrenia (Meltzer, & Massey, 2011) since many patients have not been manage by
‘dopamine’ medications only but by the drugs which affect the transmission of both serotonin
and dopamine (Dalley, & Roiser, 2012). For example, Risperdal and Clozaril.
Glutamate – glutamate is a neurotransmitter in the brain which aids to activate neurons and brain
cells. Various parts of the brain that are related to schizophrenia are linked up by brain cells
which depend on glutamate for communications. Various studies have also indicated that the
antagonists of N-methyl-d-aspartate (NMDA) subtypes of glutamate receptors may produce
symptoms similar to those of schizophrenia in healthy people and worsens the symptoms in those
with schizophrenia (Howes, McCutcheon, & Stone, 2015).
Question 3
Auditory hallucination manifestation and areas of the brain involved
Auditory hallucination is whereby an individual is able to hear sounds without auditory stimulus
(Bleuler, 2018). Some are related to mental disorders while others are related to physical brain
issues. It may however occur to individuals lacking any of the issue, but this is not common.
Auditory hallucination usually manifests in three ways; voices speaking in a person own
thoughts such that he can actually hear them, a person hearing one or more voices which are

arguing and one may also hear a voice which is narrating the actions being done by that
individual. One may also hear music, in most cases familiar songs, playing in their mind. This
usually results from having lesions on the brain stem especially as a result of stroke. This should
however be differentiated from the experience which common where a person get a song stuck in
their head.
Failure of the fronto-parietal sulcus leading to cognitive suppression was formerly known to be
the cause of auditory hallucination. New research however suggests that the left superior
temporal gyrus is involved such that misrepresentation of speech is considered a cause. It is also
thought that the left temporal lobe is involved because the neural pathways that are of concern in
the production and perception of normal speech are lateralized to the left temporal lobe.
Question 4
Medications to alleviate James’ symptoms
Antipsychotics
They are also known as neuroleptics or major tranquilizers and are mostly used to manage
delusions, hallucinations, disorganized thinking and paranoia especially in patients who have
been diagnosed with schizophrenia. They are very effective in alleviating symptoms of psychosis
in short term use. They are classified into first and second generation or typical and atypical ones
First generation are those that antagonize dopamine receptors only (D2) they include haloperidol,
risperidone and fluphenazile while second generation antagonize both dopamine and serotonin
they include clozapine and quetiapine.
Haloperidol

Side effects
Neurologic effects
This are side effects that alter extrapyramidal system which normally regulates skeletal, posture
and tone of the muscles .These leads to extra pyramidal symptoms which can be acute or
tardive .They include; tardive dyskinesia (jerky movements), dystonia(continuous spasms and
muscular contractions), akathisia (motor restlessness), Parkinsonism (rigidity), tremor and
bradykinesia(slow movements) Peluso, Lewis, Barnes, & Jones, 2012).This effects results from
the depletion of dopamine receptors which are implicated in neurologic processes, such as, fine
motor control. Haloperidol and other first generation drugs causes this effects due to their action
of antagonizing dopamine receptor. Tardive dyskinesia is due to the deficiency in cholinergic as
a result of hypersensitivity of dopamine receptors in caudate putamen in the brain
Clozapine
Metabolic and endocrine effects
Weight gain, hyperglycemic, hyperlipidemia and hyperprolactinemia are common. Weight gain
is due to the increase in cortisol level which is a characteristic for the acute periods with
psychomotor agitation. This will lead to higher resistance of insulin and hyperglycemic states
occur. Use of clozapine mostly causes these metabolic problems. Hyperprolactinemia is also
witness in women using clozapine and may lead to agalactorrhea and amenorrhea syndrome. In
some instances, infertility occurs due to high levels of cortisols.
Benzodiazepens

This is a sedative hypnotic that causes calming effect and reduce anxiety and encourage onset
and maintenance of sleep. Diazepam is the most commonly used drug. They act by binding to the
benzodiazepine site on GABA receptors resulting in a relaxed or sedated feeling caused by
depressing the activity of central nervous system
Side effects
Drowsiness
This is due to calming effect and initiation and maintenance of sleep
Central nervous system effects like confusion
Tiapride
This is a drug which may be used as an alternative for benzomide antipsychotic drug. This drug
consists of a D2 and D3 dopamine receptor antagonist activity in the locus ceruleus and limbic
brain which is selective (Egli, 2018).
Common side effects of Tiapride are extrapyramidal symptoms, drowsiness and orthostatic
hypotension. The extrapyramidal effects such as, dystonia, parkinsonism, akathisia and tardive
dyskinesia occurs when there is depletion of dopamine or dopamine blockade in the basal
ganglia.
Tiapride also causes the prolactin levels in plasma to be excess. This can result in libido
decreasing, infertility and may also increase the potential of developing breast cancer. One of the
primary roles that dopamine plays is to regulate the release of prolactin by binding to D2
receptor on the prolactin-secreting cells which is located in the anterior pituitary. These cells are

therefore disinhibited when tiapride blocks the D2 receptors leading to releases of more
prolactin.

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