PSYC62H3 Chapter Notes - Chapter 7: Malnutrition, Sympathomimetic Drug, Catechol-O-Methyl Transferase

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12 Apr 2012
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Chapter 7: Psychomotor Stimulants and Antiparkinsonian Drugs
Introduction:
Psychomotor stimulants: at low to moderate doses, these drugs produce motor stimulation,
reduce fatigue, increase resistance to sleep, increase vigilance, and alertness, and induce a
heightened mood (euphoria) or anxiety
Inverted U-shaped dose-response relationships --> increases performance up to a certain level and
then reduces it with increases in dosage
Most common drug: caffeine
Some other psychostimulants:
o Nicotine
o Amphetamines
o Cocaine
o Several DA agonists
Motor Effects of Psychomotor Stimulants
Rate dependent effects: the effect of the drug depends upon the baseline rate of response
generated by the schedule
o High rates of lever pressing (i.e. drug seeking ) under low response rate of schedules (i.e..
Fixed interval schedule)
o Lower rates of lever pressing under high baseline rates of response (i.e. fixed ratio schedule)
At low doses:
o Increase locomotor activity and exploration
At higher doses:
o Induce stereotypy (focused and repetitive behavior continued for extended periods of time)
Neurobiology:
o DA system critical for motor effects
o Double dissociation effect
Two distinct brain areas mediate two different behaviors and the effect of these areas
can dissociate this effect
Depletion of DA in the NAc --> suppress locomotor effect but no effect on stereotypy
Depletion of DA in the striatum --> suppress stereotypy (high doses)but no effect on
locomotion (low doses)
Suppressed amphetamine induced stereotypy but enhanced apomorphine
induced stereotypy
Why?
Different path of action:
Amphetamine needs DA terminals to stimulate release and block uptake
of DA
Apomorphine is an agonist
Depletion of DA is done through removal of DA producing neurons -->
causes supersensitivity of the post-synaptic neurons (increased DA
receptors)
Thus, more apomorphine can act and bind to receptors --> stereotypy
Caffeine
Most widely used behaviorally active drug
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Minor psychostimulant
Part of methylxanthines
Nonselective antagonist of adenosine receptors
Adenosine:
o Neuromodulator that effect neuronal excitability, and actions on A1 subtype of receptors,
and inhibits presynaptic neuronal release of various NTs (ACh, NE, DA, GABA, 5-HT)
o There is a functional relationship between adenosine A2A receptors and DA D2 receptors
(co-localized in the same neuron in the striatal areas)
Caffeine:
o Blocks adenosine receptors (A1) --> enhance release of NTs --> increase circulating
catecholamines
o Stimulates locomotor activity and produces rate-dependent effects on operant lever
pressing
By acting as antagonist on A2A receptors but this stimulates the DA system to produce
psychomotor stimulant effects
Caffeine is rated as having the most desirable and pleasant reactions in heavy coffee drinkers,
particularly if they have not had coffee for several hours. Caffeine abstainers are more likely to
report unpleasant reactions to caffeine.
o Thus, reinforcing effects come from the ability of coffee to terminate caffeine withdrawal
symptoms
Effect of caffeine
o Mood-elevation and fatigue-relieving (2 cups of coffee - low dose)
o Insomnia, restlessness, mild sensory disturbances, muscle tenseness, anxiety, panic attacks
(7-10 cups of coffee - high dose)
o Increase heart rate but differently in men and women
o @ Low to mod doses
dose-dependent improvements in indices of arousal, alertness, vigilance, and some
psychomotor performance and cognitive functions
Positive mood --> well-being, energy, and concentration
Increase capacity for muscular work and intellectual effort
o Biphasic (lower doses help, but high doses have no benefit/reduce performance)
o The behavioral effects of caffeine are subtle --> may depend on the person initial behavior
as a heavy consumer or not
Effects are most pronounced in low arousal states
o Caffeine + alcohol --> only the alertness increase while the symptoms of drunkenness
remain
o Caffeine + nicotine
enhances the reinforcing effect of nicotine (another stimulant)
Smokers metabolize caffeine faster
Caffeine can become a conditioned stimulus for nicotine
o Tolerance
Due to up-regulation of adenosine receptors in the brain
o Withdrawal
Uncommon except for very heavy use (~500mg/day)
Headaches
Increased fatigue, sleep, laziness
Decreased vigor and alertness
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Neonatal withdrawal symptoms may occur to infants born to mothers who consume
heavy doses
o Dependence liability is very low
o Energy drinks --> contains a very high caffeine content
Lead to caffeine intoxication
Nicotine
Acts as a nicotinic ACh agonist
Cigarette = vehicle for nicotine administration
Large majority of adult smokers began in their adolescence
o Predictors of starting smoking at adolescence:
Male
White
Positive attitudes towards smoking
Concern over body weight
Positive perception on outcomes of smoking
Low expectation of school achievement
Ease of access to tobacco
Number of smoking friends
Lower self-esteem
Perceive to have less control of their lives
Higher levels of trait anxiety
o Genetic predispositions:
Depressive disorder --> odds of nicotine dependence increase by 2.3 times
o Depression can also be a symptom of the withdrawal itself
Initial experience is a negative one, but external pressures cause a person to continue use and
develop a dependence
Nicotine is not the only factor leading to repeated use
o Nicotine reduces negative affect (and its withdrawal symptoms) --> continue smoking
o Nicotine affects social image (acceptance by peers etc.) --> continue smoking
Effects of nicotine
o Low doses --> enhancement of mood and drug liking
o High doses --> aversive effects
o Increase extracellular and synaptic concentrations of DA in NAc (associated with primary
reward)
o Mild psychostimulant effect --> esp. increased vigilance
o People report cigarette calms them down and reduces tension (b/c it stops withdrawal
symptoms
o Factors:
Whether the person is a tobacco user or not
Degree of nicotine dependence and deprivational level at time of testing
Route of administration --> affects onset and duration
Dose (typically U-shaped dose-response function)
Pre-drug psychological state
Type of task used in testing
o Enhance sustained attention and recognition memory
Nicotine stimulates nAChRs (these receptors are found throughout CNS)
o PNS --> sympathomimetic effect (primarily release of Ad) and some parasympathetic effects
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