Chapter 10: Psychomotor stimulants

Question 1

Why are psychomotor stimulants considered to be sympathomimetic drugs?

Answer 1

considered to be sympathomimetic drugs because epinephrine is the primary transmitter of the sympathetic (fight or flight) nervous system, and thus these stimulants stimulate sympathetic nervous system and mimc sympathetic arousal.

Question 2

What is the primary transmitter of the sympathetic nervous system?

Answer 2

epinephrine

Question 3

type of transmitter psychomotor stimulants affect?

Answer 3

catecholamines (DA, NE, E) and indolamines (serotonin)

Question 4

Why is rate of absorption slowed if psychomotor stimulants are taken orally?

Answer 4

because psychomotor stimulants are WEAK BASES and are thus IONIZED in the acidic digestive system, making them less lipid soluble and thus absorption is slowed.

Question 5

advantage of oral administration of amphetamines

Answer 5

slow absorption allows blood levels to be kept fairly constant.

Question 6

factors that affect digestive system absorption of amphetamines

Answer 6

1) physical activity

2) food in stomach.

Question 7

what is the limiting factor of the rate of absorption in intranasal cocaine administration?

Answer 7

cocaine is a vasoconstrictor and thus will decrease the surface area to which it can be absorbed into the blood stream

Question 8

metabolism of amphetamines mainly occurs in the ____, and excretion depends on how _____ the urine is.

Answer 8

metabolism of amphetamines mainly occurs in the LIVER, and excretion depends on how ACIDIC the urine is. the more acidic the urine, the less reabsorbion occurs and thus more is excreted.

Question 9

metabolism of cocaine occurs ____ than amphetamines, and mainly occurs in the ____ and ___ with the help of _____ (type of enzyme).

Answer 9

metabolism of cocaine occurs FASTER than amphetamines, and mainly occurs in the LIVER and BLOOD with the help of CHOLINESTERASES (type of enzyme).

Question 10

Why might psychomotor stimulants effects last a very long time past the expected half lives of the original stimulants?

Answer 10

they might have active metabolites with long half lives.

Question 11

Two methods that monoamines are removed from the synapse/stop affecting receptors

Answer 11

1) being broken down by MAO or COMT

2) reuptake via transporters. DET for dopamine, NET for epinephrine, and SERT for serotonin reuptake

Question 12

In addition to the transmitter, what else does the transporter need to be bound to in order for the transmitter to be taken back into the neuron?

Answer 12

transporters are Na+/Cl- dependent substrate specific neuronal membrane transporters. they need Na+ and Cl- to bind to the transporter in order for it to work

DET: needs 2 Na+ and 1 Cl-
NET and SErt: needs 1 Na+ and 1 Cl-

Question 13

After being transported back into the cells via their respective transporters, the monoamines are stored in vesicles with the help of _____ in order for storage for next time they are needed in the synapse.

Answer 13

After being transported back into the cells via their respective transporters, the monoamines are stored in vesicles with the help of VESICULAR MONOAMINE TRANSPORTER in order for storage for next time they are needed in the synapse.

Question 14

How does cocaine effect monoamine transmitters and their respective synapses?

Answer 14

reuptake inhibitor: binds to the RECEPTOR site of the TRANSPORTER so that it is unable to transport monoamines back into the cell – DA, NE, ST all stay in the synapse longer

Question 15

How do amphetamines effect monoamine transmitters and their respective synapses?

Answer 15

amphetamines are SUBSTRATE TYPE RELEASERS; indicating that they are structural analogues of monoamines. They bind to the transporter (along with Na+ and Cl-) and get packaged into vesicles in the presynaptic neuron. Reabsorption of monoamines slows down because it is competing with the drug for transportation, and therefore, the monoamines hang out in the synapse for longer periods of time.

Question 16

In addition to competing with the monoamines with transportation back into the cell, how else do substrate type releasers affect monoamines and their respective structures (transporters, synapses etc).

Answer 16

1) amphetamines disrupt PH balance in the vesicle and inhibits VMAT function- preventing the repackaging of monoamines therefore monoamines cannot get stored into the synapse== vesicles thus get triggered to release monoamines into the cytoplasm because of the pH change.

2) amphetamines/substrate type releasers REVERSE the direction of transporters, moving monoamines out of the cell at a higher rate.
- allows transmitters to be pushed into the synapse without needing an action potential.

3) amphetamines also inhibit the activity of MAO; monoamines remain in the cleft longer.

Question 17

T/F amphetamines are substrate-type releasers are affected by AUTORECEPTORS and can thus be stopped

Answer 17

False. substrate-type releasers are not affected by autoreceptors. autoreceptors can detect monoamine levels, and modulate how much are being released. They can modulate transport blockers, but not substrate type releasers sub-type releasers can release transmitters into the synapse without action potentials.

Question 18

which transporter is affected by cocaine the most?

Answer 18

all monoamine transporters are affected equally by cocaine

Question 19

Which transporter and thus neurotransmitter is affected by amphetamine the most?

Answer 19

amphetamine binds to NET more preferentially, and thus epinephrine is affected the most.

Question 20

cocaine is an _____ agonist of DA, NE and 5HT because the drug does not act as a structural analogue of the neurotransmitters

Answer 20

cocaine is an indirect agonist of DA, NE, and 5HT. it is indirect because they do not substitute for the Da/NE, they facilitate transmitter activity in the synapses.

Question 21

although all monoamines are affected by psychomotor stimulants, most behavioral affects are the results of increased activity on _____

Answer 21

dopamine systems.

Question 22

name the 3 dopamine systems of the CNS

Answer 22

1) Nigrostriatal dopamine system- runs from substantia nigra to striatum
2) Mesolimbic dopamine system- runs from VTA to Nuc.Acc.
3) Tuberofunibular dopamine system- controls secretions from the pituitary gland.

Question 23

how do psychomotor stimulants affect the PNS

Answer 23

stimulates the PNS (sympathetic fight or flight nervous system) by increasing the amount of epinephrine in the synapses.

Cocaine can also act as a local anaestethic by blocking Na+ and K+ channels, which blocks the conduction of action potentials

• constriction of blood vessels also seen because of increased epinephrine availability, which facilitates the contraction of smooth muscle

Question 24

How does cocaine that is administered through the skin act as a local anaesthetic?

Answer 24

Cocaine can also act as a local anaestethic by blocking Na+ and K+ channels, which blocks the conduction of action potentials

Question 25

How do psychomotor stimulants constrict blood vessels?

Answer 25

constriction of blood vessels also seen because of increased epinephrine availability, which facilitates the contraction of smooth muscle

Question 26

What kind of symptoms arise from sympathetic nervous system arousal due to psychomotor stimulants?

Answer 26

increased HR, BP, VASODILATION and BRONCHODILATION.

Question 27

why can psychomotor stimulants lead to heart failure?

Answer 27

psychomotor stimulants activate the sympathetic nervous system by increased epinephrine. the body needs more oxygen in order to facilitate all the fight or flight stuff, causing increasing BP and HR, causing WEAKENING OF Blood vessels, causing heart failure

Question 28

T/F: effects of amphetamines are expressed greater in groups than when the person is alone

Answer 28

True

Question 29

Which receptors are effected that cause a reduction in appetite?

Answer 29

due to serotonin receptors 5-HT1b, 5-HT2c activation by the stimulants.

Question 30

how to psychomotor stimulants affect sleep?

Answer 30

they block fatigue due to increased activation of epinephrine, dopamine etc and they INCREASE concentration. they reduce REM sleep.

Question 31

psychomotor stimulants often produce positive rating scales. What’re some positive ratings?

Answer 31

euphoria, increased energy, higher work ethics.

Question 32

cocaine induced euphoria causes decreases in neural activity. how was this proven?

Answer 32

PET scans shows less glucose metabolism going on in the hippocampus, basalganglia and thalamus.

Question 33

do psychomotor stimulants show acute tolerance?

Answer 33

yes, subjective effects tend to be greater when blood levels are increase rather than decreasing.

Question 34

what is a rush? what brain structures are active during a rush?

Answer 34

both amphetamine and cocaine produces intense feelings of euphoria and pleasure, causing a rush. there is increased activity in parietal and occipital lobes.

Question 35

what is punding? whats it caused by?

Answer 35

a stereotypical behavior seen by performing repetitive tasks for an extended period of time, caused by STIMULATION of the NIGROSTRIATAL DOPAMINE SYSTEM, which has input to the EXTRAPYRAMEDAL MOTOR SYSTEM.

Question 36

Define Psychomimetic effects, what are these effects caused by?

Answer 36

schizophrenia-life psychosis from prolonged use of psycho-motor stimulants. Delusions are caused by INCREASED DA ACTIVITY, similar to schizophrenia. The drug arrives in high concentrations to the brain (BOLUS EFFECT) due to enzyme kinetics.

may include delusions of persecution “their own to get me,” hostility and violence, paranoia, hallucinations.

Question 37

parasitosis

Answer 37

the feelings of bugs crawling around the skin

Question 38

amphetamine ____ the critical frequency of fusion threshold, showing increased visual acuity

Answer 38

amphetamine LOWERS the critical frequency of fusion threshold, showing increased visual acuity

Question 39

What did the digital symbol substitution test show about amphetamine’s performance effects?

Answer 39

the digit symbol substitution test tested short term memory and reaction speed. demonstrated that people on amphetamine had increased performance and decreased reaction time

Question 40

what did the clock task show about amphetamine’s performance effects?

Answer 40

amphetamine uses were able to focus longer and thus attention span increased, they were also able to remain vigilant for longer periods of time, therefore fatigue was reduced.

Question 41

Although generally amphetamines show increased attention span, they often can only focus on one event at a time and miss other things. why?

Answer 41

often due to TUNNEL VISION. they only focus on one thing at a time.

Question 42

T/F: amphetamine has the ability to improve performance in tasks that require vigilance of prolonged attention, as well as improving performance when weird adverse factors are happening, like decreased oxygen levels.

Answer 42

true.

Question 43

How do amphetamines treat ADHD?

Answer 43

ADHD arises from DECREASED monoamine levels in prefrontal cortex in areas used to mediate attention. Amphetamines tend to increase dopamine and NE activities by acting as a subtstrate-type releaser, improving attention and impulse control.

Question 44

What are two reasons as to why psychomotor stimulants facilitate weight loss?

Answer 44

1) effect of the drug on part of the brain responsible for appetite control
2) drug increases locomotive behavior and reduces the time available for eating and drinking.

• another reason may because of changes in Serotonin functions. 5-HT1b and 5-HT2c

Question 45

describe the rate dependency effect

Answer 45

affects conditioned behavior. methamphetamine increases the rate of responding if it was low, but slowed responding that was normally fast. punishment-suppressed behavior does not increase in frequency when animal is exposed to amphetamines.

Question 46

Do psycho-motorstimulants have high reinforcing effects?

Answer 46

yes. people will readily self-administer psychomotor stimulants like cocaine. they will work very hard to get.

Question 47

What do psycho motor stimulants generalize to? what kind of drugs can be discriminated from psychomotor stimulants?

Answer 47

psycho motor stimulants generalize to other amphetamines, cocaine and MAO inhibitors

psycho motor stimulants DO NOT GENERALIZE to caffeine, barbituates, nicotine etc.

Question 48

T/F: psycho motor stimulants generalize to other stimulants such as caffeine and nicotine

Answer 48

FALSE.

Question 49

How can you block the discriminative effects of psycho motor stimulants, allowing them to generalize to things they would not normally generalize to?

Answer 49

discriminative effects can be blocked using D1 and D2 blockers in the mesolimbic dopamine system.

Question 50

Which receptors must you block in order to diminish the discriminative effects of psycho motor stimulants?

Answer 50

the mesolimbic dopamine system, not the nigrostriatal.

Question 51

Which symptoms exhibit tolerance with chronic use? which symptoms of psycho motor stimulants show sensitization? what system is responsible for the sensitization?

Answer 51

lethal doses show tolerance. chronic amphetamine users are able to increase their dose to extremely high levels.

sensitization takes place in terms of the LOWERING of threshold for CONVULSIONs. Chronic cocaine use lowers thresholds for colvulsions, sterotyped behavior and spontaneous motor activity.

sensitization is a result of increased sensitivity of the MESOLIMBIC dopamine system.

Question 52

What is the most prominent characteristic of psycho motor stimulant withdrawal?

Answer 52

depression. occurs faster with cocaine, may take a couple days to show for amphetamines.

Question 53

Why may withdrawal of psycho motor stimulants cause decreased performance?

Answer 53

caused by reduced PFC activation, and a failure to activate the ventromedial cortex. PFC activation is usually associated with critical thinking, thinking under pressure, and decision making. decreased activity in this structure results in poor performance.

Question 54

T/F individuals who have used cocaine at the same dose for a longer time will have worse withdrawal symptoms than an individual who has used cocaine at the same dose for a shorter period of time.

Answer 54

FALSE. individuals who experience more intense highs from cocaine tend to suffer more severe withdrawal symptoms. it is not about duration of use, its about dose.

Question 55

what kind of cycle is cocaine self administered in in humans?

Answer 55

typically administered via the run-abstinence cycle: cocaine is usually binged in large quantities followed by periods of abstinence.

Question 56

Describe the run way task model.

Answer 56

studied self administration in non humans. animals tend to fear cocaine, but will run faster to get the cocaine. animals are afraid for something they want.

Question 57

Describe cue induced reinstatement, what does this exhibit?

Answer 57

put rat in box with 2 levers; one administers cocaine and the other is a dead lever. You then deactivate the cocaine lever. however, even though the lever no longer gives cocaine, rats will press it more than the other- rats will remember that the lever used to provide cocaine for up to 9 months.

proof of hedonic dysregulation.

Question 58

describe stress-induced reinstatement.

Answer 58

cocaine response will increase when stressed. only in animals that have cocaine experience. cocaine thus changes the relationship between stress and reward in the brain. Stress and reward now interact, and therefore the INCENTIVE OF COCAINE NOW GETS INTENSIFIED

read notes

Question 59

what is the mechanism of stress-induced reinstatement?

Answer 59

CRF antagonism attenuates shock-elicited lever responding (i.e.stress-induced reinstatement) and also reduces glutamate and dopamine release from the ventral tegmental area(VTA)

Question 60

describe how brain damage contributes to psychosis as a harmful effect of prolonged use of psycho motor stimulants

Answer 60

• irreversible brain damage that has also been reported as a result of deterioration and rupturing of small blood vessels in the brain
• damage to dopamine neurons in the STRIATUM: cell death may contribute to psychosis.
• cell death of GABA interneurons

Question 61

what is a cain reaction?

Answer 61

the 2 phases of overdose.

1) severe headaches, nausea and vomiting
2) convulsions, loss of conciousness, respiratory depression and cardiac failure.

Question 62

describe the neurotoxic effects of psycho motor stimulants

Answer 62

• prolonged cocaine use is associated with decreased grey matter.
• prolonged used causes the enhancement of all 3 DA pathways, causing excessive glutamate release, causing damage to GABA interneurons because they have a lot of NMDA receptors, causing glutamate dysregulation in the cortex, which leads to psychosis.

less GABA interneurons= glutamate dysregulation= more cell death because too much or too little NMDA receptor activation results in cell death.