Exam Textbook Notes 7, 10, 12, 13

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23 Apr 2012

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- At low to moderate does, these drugs produce motor stimulation, reduce fatigue, increase resistance to sleep,
increase vigilance and alertfullness, induce heightened mood
- The dose response functions typically are inverted U shaped
- Other used terms for these drugs are behavioural stimulants and CNS stimulants
- Caffeine is the most used psychostimulant
- Next is nicotine
- Nicotine and caffeine, along with other substance are referred to as minor stimulants
- Amphetamines, Ritalin, cylert, cocaine, and several DA agonists are grouped as major stimulants
Motor effects of psychomotor stimulants
- Stimulants produce rate dependent effects on responses the effect of the drug depends upon the baseline rate
of response generated by the schedule
- Stimulants also produce motor effects, like increased locomotor activity and exploration
- As dose gets higher, stimulants produce less in the way of locomotion and instead induce a response known as
o Stereotypy refers to focused and repetitive gnawing in rodents
o Also seen in non-human primates, referred to as punding
- Forebrain DA systems are critical for the expression of the motor stimulant effects of major psychomotor
- Susan Iversen et al, lesions were produced by local injections of the neurotoxic agent 6-hydroxydopamine, which
enters into the terminals of catecholamine neurons and then depletes DA by killing the entire cell or destroying
the terminals
o Depletion of DA supressed locomotor stimulant effects of low doses of amphetamine but did not
supress stereotypy with high doses
o Depletion of DA in neostriatum reduced stereotypy but not locomotion
o “double dissociation
- Another behavioural manifestation of receptor super sensitivity seen after DA depletion was observed in
experiments involving the rotation model
o A unilateral DA depleted is produced, and administration of stimulants causes and asymmetrical
locomotion known as rotation or circling
- One of several substances referred to as methylxanthines
- Typical American adult consumes 200mg 300mg of caffeine a day
- It is difficult to determine the overall time course and impact of caffeine on an individual due to excretion,
absorption, and metabolization variability
- Most of its effects are related to its ability to act as a nonselective antagonist of adenosine receptors
- Adenosine acts as a neuromodulator that affects neuronal excitability and actions on the A1 subtype of
receptor, and inhibits presynaptic neuronal release of a variety of neurotransmitters
- Caffeine is rated as having desirable and pleasant reactions in heavy coffee drinkers, and coffee abstainers are
more likely to report unpleasant an undesirable reactions to caffeine
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o Suggests many of the reinforcing effects of caffeine stem from its ability to terminate caffeine
o Avg caffeine intake of coffee consumers doesn’t predict the occurrence of withdrawal
o When coffee consumers are tested with caffeinated or decaffeinated coffee (without knowing), they are
more likely to self-administer caffeinated than decaffeinated coffee
o Two cups of coffee = 150 mg of caffeine, has mood elevating and fatigue relieving effect
o 7-10 cups can cause caffeinism (insomnia, restlessness, muscle tension)
o Caffeine may not increase all indexes of arousal or change hem in the same way in all personas
o As little as 32 mg of caffeine has been shown to significantly improve auditory vigilance and visual
reaction time
o Effects of caffeine on endurance are biphasic, at low doses they enhance performance but at high doses
have no effect/lower performance
o Caffeine can enhance reinforcing and subjective stimulant qualities of nicotine in humans
Smokers metabolize caffeine at an accelerated rate than non-smokers
Upon quitting smoking, caffeine can increase caffeine plasma levels by 200%, causing jitteriness
Withdrawal symptom of smoking
o Consumption of high doses of caffeine spurred on by growing consumption of energy drinks has led to
increasing reports of caffeine intoxication
- A wide variety of studies have indicated that there are numerous predictors of adolescent tobacco use
o Being male, white, holding positive attitudes towards smoking, concerns over body weight, parents who
smoke, peer pressure,
o Nicotine dependency strongly associated with alcohol dependency, which has an established linkage to
o Nicotine dependent persons are more than twice as likely as nondependent nicotine uses to have
suffered from major depression
o The psychosocial rewards such as peer acceptance and role model identification are sufficiently strong
to maintain smoking behaviour until the individuals learn to monitor the amount of smoke and the
unpleased side effects subside
o Debate whether nicotine is the principal reinforce (chewing nicotine gum doesn’t have the same effect)
o Studies showed that the number of cigarettes smoked was inversely related to the nicotine content, not
tar content
o Effects of nicotine on performance are variable and subtle
Many factors involved:
Whether person being tested is a tobacco user or not
The degree of nicotine dependence and deprivation level at the time of testing
The route of an administration
The dose
The pre-drug psychological state of the person
The type of task used
o Smokeless tobacco is not harmless
Associated with oral and pharyngeal cancer, dental& gum problems, and cardiovascular
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Amphetamines and related drugs
- Exert more intense and distinct emotional and cognitive effects
- Methcathinone is the newest of potent amphetamine related psychostimulants to be introduced into the US
and is as addictive as crack cocaine
o Company abandoned research and then a student stole a sample of it and its manufacturing process and
then sold it to the illicit market
o But there was no demand for this product because its effects were the same as cocaine
Behavioural effects of amphetamines
- Most striking beneficial effects are noted when the person is fatigued
- May also enhance performance on tasks involving strength and endurance due to their sympathomimetic
- ARDs reduce frequency of other activities while increasing other kinds of activities
o I.e. Undifferentiated motor activity in observed children with ADD may be reduced with
psychostimulants because they enhance on-task activity
- Adults report enhanced moos and arousal
- Exposure to higher doses can precipitate a psychosis with symptoms similar to paranoid schizophrenia
- May engage in violence, suspicion, philosophical concerns
- Rats bob their heads and display gnawing behaviours
- Monkeys exhibit grooming like movements of body and limbs
- Chimps rock back and forth
Clinical uses of amphetamine
- Following its use in treatment of asthma, amphetamine’s first clinical uses for its CNS effects was in treatment of
narcolepsy, a disease where the person falls asleep repeatedly during the day without warning
- Then it was used for ADD
- Armed forces gave amphetamine to its soldiers debatable as to whether this helped or hurt them
- Supposedly Hitler used amphetamines
Pharmacokinetics and pharmacodynamics of amphetamines
- High in lipid solubility and can be inhaled, taken orally, or injected thru IV administration
- Can be smoked in the form of methamphetamine hydrochloride (aka ice)
- Amphetamines increase extracellular concentrations of the monoamines thru two primary mechanisms, both of
which involve the protein transporters that normally terminate the action of monoamines via reuptake
o 1. They bind to these transporters and inhibit monoamine reuptake into neurons
o 2. They promote reverse transport of monoamines, meaning they induced the release of monoamines
from neurons thru these transporters
- Amphetamine and its derivatives differ primarily in terms of their potency in these two processes, as well as
their potency of affecting the three monoamine transporters
Dependence on amphetamines
- In early 70s amphetamine was very popular and very easy to obtain
- Mid 70s began to decrease
o Gov’t exerted legal pressures on pharmaceutical companies to decrease their production
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