Stimulants (Test 2)

Question 1

Monoaminergic stimulants

Answer 1

Increase synaptic levels of monoamine transmitters (especially dopamine and norepinephrine) to mediate stimulant and rewarding properties

Question 2

Some of the earliest reasons that people would routinely take amphetamines/cocaine in the early days?

Answer 2

Increased attention and mood at low doses

○ Used to give amphetamines to people to get them to do boring and tedious tasks and stay attentive. Increased arousal and vigilance.

Question 3

Effects of amphetamines/cocaine at higher doses

Answer 3

Get decreased activity and mood, can lead to schizophrenia like state (positive symptoms)

Question 4

How do amphetamines/cocaine have a biphasic effect

Answer 4

Early stimulant, later depressant effect when looking at locomotion

Question 5

Why is there a decrease in the “biphasic” effect

Answer 5

• Dopamine used to initiate motor sequences.
• Used to measure activity with mice in a box with IR lasers, counted how many beams the mouse broke while running around.
• A decrease in locomotion because you activated motor movements to the point where you can’t activate a full sequence and you’re stuck in one movement chain

Question 6

How is decrease in activity due to stimulants related to schizophrenia?

Answer 6

• Also common in people with schizophrenia because they have too much dopamine activation.
• Small, repeated movements didn’t break enough laser beams, made people think that it was a depressant effect when really it’s stimulation to the extreme.

Question 7

Do stimulants eventually become sedatives?

Answer 7

Decreased activity, but not sedative. Too much stimulation.

Question 8

What happens with repeated administration of amphetamines/cocaine at postsynaptic sites?

Answer 8

Reinforcing effects gain tolerance. This means your doses get progressively bigger due to down-regulation at postsynaptic sites.

Question 9

What happens with repeated administration of amphetamines/cocaine at presynaptic sites

Answer 9

Motor and psychosis effects sensitize and get bigger each time you take the drug due to downregulation at presynaptic autoreceptors.

Less sensitive autoreceptors, less inhibition of NT release. Causes excessive release of dopamine.

Question 10

stereotopy

Answer 10

small, repeated movements.

Question 11

How are amphetamines usually taken?

Answer 11

Usually orally or inhaled

Question 12

Amphetamine pharmacokinetics

Answer 12

• High lipid solubility
• Weak base, best absorbed in the small intestine
• Huge half-life, from 1/3 of a day to a day and a half

Question 13

What is amphetamine metabolized by?

Answer 13

Metabolized in the liver by cytochrome P450, shows cross tolerance with other drugs

Question 14

TI for amphetamine?

Answer 14

rough TI is 7-15

Question 15

Cocaine pharmacokinetics

Answer 15

• Poorer absorption than amphetamine, less lipid soluble.

- Half-life of about 60 minutes. Has a much shorter effect than amphetamine

Question 16

What is cocaine metabolized by?

Answer 16

Metabolized by cytochrome P450

Question 17

What is the TI for cocaine?

Answer 17

TI is roughly 15, double digits. On border of what we’d define as a very dangerous drug. Want TI to be in at least double digit domain. Potentially lethal consequences.

Question 18

Amphetamine pharmacodynamics

Answer 18

• phosphorylates dopamine transporters so DA is pumped out of the cell into the synapse.
• With amphetamine, you don’t need Ca for exocytosis. DA is pumped into the synapse anyways. It’s Calcium independent and doesn’t need action potentials.

Question 19

Cocaine pharmacodynamics

Answer 19

• Only blocks monoamine transporters (doesn’t reverse transportation). esp. 5-HT and dopamine
• This means that cocaine needs action potentials to work.
• local anesthetic by blocking voltage-gated ion channels including (voltage gated sodium channels)

Question 20

monoamine transporter

Answer 20

Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters

Question 21

How was cocaine used originally?

Answer 21

Doctor friend realized that it’s a local anesthetic and blocks conduction of pain. Analogues are now used for this (lidocaine for dentistry)

Question 22

Primary reinforcing effects over time

Answer 22

Primary reinforcing effects usually diminish over time and become less important the more that people take a drug.

Question 23

what is a primary reinforcer?

Answer 23

a primary reinforcer is a stimulus that does not require pairing to function as a reinforcer and most likely has obtained this function through the evolution and its role in species’ survival. Examples of primary reinforcers include sleep, food, air, water, and sex.

Question 24

Does stress raise dopamine levels?

Answer 24

Stress increases dopamine – for this reason, perhaps, people who are stressed take drugs. Increase in dopamine might lead to the user having more reinforcing thoughts/behaviors

Question 25

Tolerance

Answer 25

addicts come to experience pleasure less

Question 26

Sensitization

Answer 26

addicts crave the experience more

Question 27

What is an example of the resiliency of monoaminergic neurons?

Answer 27

Monoaminergic neurons are resilient – in parkinson’s you don’t see symptoms until about 50% of the neurons are gone

Question 28

What is Ibogane?

Answer 28

Ibogane – a new psychotropic, this drug is an oneirogen, a drug that leads to an altered state of consciousness in which a person is amenable to behavioral modification via some form of cognitive therapy.

Question 29

Incentive-motivation model of addiction

Answer 29

The incentive salience [incentive-moitvation] theory of addiction suggests that “liking” (hedonic value) of a drug may be dissociated from “wanting” the drug due to increased incentive salience.

Question 30

amphetamines and ADHD

Answer 30

amphetamine and related stimulants reduce the symptoms of ADHD by increasing the “signal-to-
noise” ratio at synapses.

Question 31

“noise” as in signal-noise

Answer 31

by blocking the DAT, “noise”

is reduced by a cAMP alteration in ion channels, primarily K+ channels.

Question 32

“signal” as in signal-noise

Answer 32

by blocking the NeT, “signal”

is increased at synapses in the PFC as NE increases the effect that transmitters like GLU have at their synapses.