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Chapter 7

Chapter 7 Psychomotor Stimulants and Antiparkinsonian Drugs.docx

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Suzanne Erb

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 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 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
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