Psychology 2020A/B Chapter Notes - Chapter 4: Stimulant Psychosis, Cocaine Dependence, Dopamine Transporter
22 May 2018
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Psych 2020
Chapter 4
Cocaine and Amphetamines
The History of Cocaine
- Cocaine - an extremely potent and dependence-producing stimulant drug derived from the coca
leaf
- Comes from small leaves of the coca shrub (~2% cocaine)
- First the coca leaves were chewed
- They still do this to this day
- But very few instances of toxicity or abuse
o Bc its in very low doses
o Absorption from the digestive system is slow
o So little cocaine enters the blood
- Availability of coca paste
o Contains much higher % of cocaine mixed with tobacco
o Smoked as a cigarette
o More likely to produce abuse and dependence
Cocaine in the 19th Century
- By the late 1850s, the active ingredient of coca plant was chemical isolated
- Cocaine has local anaesthetic effects
- Cocaine inhibits voltage gated Na+ channels
o This can prevent sensory receptors on the tongue from sending messages to the brain
- Then it started to become popular to mix cocaine and wine
o Now we know that combination of alcohol and cocaine produces a metabolite with an
elimination half life up to 5X longer than that of cocaine alone
o Sot he intoxicating mixture lasts longer
- Then celebrities started to endorse it
Freud and Cocaine
- Freud had depression
- He tried cocaine and loved it
- He started to give it to other people
- His friend became dependent and started to increase his cocaine dose to 20X what friend was
taking
o He then developed cocaine induced psychosis and then developed formication
o Formication – hallucinatory behavior produced by chronic cocaine or amphetamine
abuse, in which the individual feels insects or snakes crawling either over or under the
skin
How Cocaine Works in the Brain
- Cocaine increases the level of neurotransmitters norepinephrine, serotonin and dopamine in the
synaptic cleft
- It does this by inhibiting transporters on the membrane of the presynaptic terminals of the
norepinephrinergic, serotoninergic and dopaminergic neurons
- Recall: it’s the role of the transporter to take up the neurotransmitter into the presynaptic
terminal
- As a result of blocking these transporters, more neurotransmitters remain in the synapse and
can bind to their respective receptors
- The structure of cocaine does not look like dopamine, so we don’t know why cocaine blocks its
reuptake so effectively
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- Cocaine has a different affinity for transporters
o greatest affinity for the serotonin transporters
o least affinity for norepinephrine transporters
- the acute effect of euphoria experiences through cocaine is directly related to an increase in
dopamine activity in the region of the brain that controls pleasure and reinforcement in general:
the nucleus accumbens
- conditioned place preference:
o technique used by researchers to test how rewarding cocaine is in genetically modified
animals
o placing a rodent in a particular arena with 2 distinct sides that have diff textures on the
floor
o then the researchers administer either the drug only when the rodent is in a particular
side or allow the rodent to self administer the drug only in one side
o after many of these training sessions, they allow the effects of the drug to wear off and
the drug free rodent is placed back into the arena and gets to choose which side it
prefers
o drugs that are rewarding and produce addiction in humans (ex: cocaine, heroine,
nicotine) all produce a CPP in rodents →they prefer the side where they previously
were given the drug
o when the dopamine and serotonin transporters were knocked out together in mice, they
no longer show CPP for cocaine
o this means that these transporters are necessary for the CPP to occur
- another study showed that the dopamine transporter alone is necessary for rats to continue to
self administer cocaine
- SO dopamine transporter is important in rewarding and reinforcing effect of cocaine and the
serotonin transporter has potential importance
How Cocaine Works in the Cardiovascular System
- Cocaine also works in the peripheral nervous system on SYN nerve fibers to stimulate the CV
system
- Cocaine blocks the reuptake of norepinephrine in the heart, causing heart to contract and HR to
increase
- Cocaine is a vasoconstrictor so it also causes and increase in BP
- In regular users, the increase in HR and BP can cause cocaine induced chest pain
- In higher doses, cocaine can act as a anaesthetic by blocking voltage dependent Na+ channels in
cardiac cells
o This can lead to arrhythmia (irregular heartbeat)
- Long term cocaine use = damage to CV health and increase probability of stroke and congenital
heart failure
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Acute Effects of Cocaine
- Powerful burst of energy
- If injected intravenously or smoked, the extremely intense effect is felt within a matter of
seconds and lasts only 5-10mins
- If snorted, the effect is less intense but lasts longer
- Also experience a sense of wellbeing (or overconfidence)
- Sometimes causes panic attack
- As levels of cocaine diminish, the mood changes dramatically (person becomes irritable,
despondent and depressed)
- The after effects are uncomfortable enough to produce a powerful craving for another dose
- chronic cocaine use causes decreased sexual performance and a loss of sexual desire
- cocaine produces sudden elevation in SYN
- powerful sympathetic changes can lead to CV problems
o CV effects are the most significant medical consequence of cocaine use
- The extreme effects of cocaine on bodily organs (esp the heart) stem from its ability not only to
excite the SYN but to inhibit the PSYN
Chronic Effects of Cocaine
- Repeated and continued use of cocaine produces undesirable mood changes that can be
alleviated only when the person is under the acute effects of the drug
- Chronic cocaine abusers are…
o Irritable
o Depressed
o Paranoid
- Long term abuse can cause the hallucinatory experience of formication (cocaine bugs)
- Formication and feelings of anxiety and paranoia cause a mental disorder called cocaine
psychosis
- Cocaine psychosis - a set of symptoms, including hallucinations, paranoia, and disordered
thinking, produced by chronic use of cocaine
- when snorted, cocaine causes bronchial muscles to relax and nasal blood vessels to constrict
o the opposite occurs when the drug wears off
o as bronchial muscles contract and nasal blood vessels relax, they have a stuffy/runny
nose and bleeding of nasal membrane
o septum of nose can develop lesions or become perforated with small holes →breathing
problems
- chronic cocaine use leads to loss of 20% of dopamine receptors
- chronic cocaine users develop the kindling effect – phenomenon in the brain that produces a
heightened sensitivity to repeated administrations of some drugs, such as cocaine
o this heightened sensitivity is the opposite of the phenomenon of tolerance
o this makes cocaine very dangerous bc cocaine has the potential for setting off brain
seizures
o repeated exposure to cocaine can lower the threshold for seizures →through a
sensitization of neurons in the limbic system over time
o so due to the kindling effect, deaths from cocaine overdose may occur from relatively
low dose levels
Medical Uses of Cocaine
- when applied to the top of the skin, cocaine has the ability to block the transmission of APs
coming from sensory receptors, preventing any sensation from that area
- cocaine can be used as an anesthetic for nasal, tear duct, and throat surgery
- other anesthetics are preferred
- disadvantage:
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Cocaine - an extremely potent and dependence-producing stimulant drug derived from the coca leaf. Comes from small leaves of the coca shrub (~2% cocaine) They still do this to this day. But very few instances of toxicity or abuse: bc its in very low doses, absorption from the digestive system is slow, so little cocaine enters the blood. Availability of coca paste: contains much higher % of cocaine mixed with tobacco, smoked as a cigarette, more likely to produce abuse and dependence. By the late 1850s, the active ingredient of coca plant was chemical isolated. Cocaine inhibits voltage gated na+ channels: this can prevent sensory receptors on the tongue from sending messages to the brain. He started to give it to other people. Cocaine increases the level of neurotransmitters norepinephrine, serotonin and dopamine in the terminal synaptic cleft. It does this by inhibiting transporters on the membrane of the presynaptic terminals of the norepinephrinergic, serotoninergic and dopaminergic neurons.
