Drugs and the Brain

definitions of drugs

• substance or mixture of substances which has been found by animal experimentation and clinical experience to be of clear therapeutic value for treating human disease

• chemical substance used for its effects on bodily processes

what sites can drugs affect the nervous system at

• receptors

• enzymes

• ion channels

• nuclear receptors

• DNA

• transporters

steps of neurotransmission

1. action potentials arrive at axon terminal

2. voltage gated Ca2+ channels open

3. Ca2+ enters the cell

4. Ca2+ singals to vesicles

5. vesicles move to the membrane

6. docked vesicles release neurotransmitter by exocytosis

7. neurotransmitter diffuses across the synaptic cleft and binds to receptors 

how do majority of neuroactive drugs effect nervous system

modulate the way synaptic transmission occurs

agonists

activates a receptor

antagonists

blocks a receptor from becoming active

ways that drugs can effect synaptic transmission

1. drug serves as a precursor

2. drug inactivates synthetic enzyme; inhibits synthesis of NT

3. drug prevents storage of NT in vesicles

4. drug stimulates release of NT

5. drug inhibits release of NT

6. drug stimulates postsynaptic receptors

7. drug blocks postsynaptic receptors

8. drug stimulates autoreceptors; inhibits synthesis/release of NT

9. drug blocks autoreceptors; increases synthesis/release of NT

10. drug blocks reuptake

11. drug inactivates acetylcholinesterase

how does cocaine affect neurotransmission

blocks dopamine transports (preventing reptuake)

how does amphetamine block neurotransmission

reverses and blocks dopamine transporters

• whatever dopamine you make in pre-synaptic is completely dumped out, doubles the dopamine in the synaptic cleft

how does alcohol affect neurotransmission

potentiates GABA receptors

• binds to gaba receptors and keeps them open for a long time, chloride goes in

how does LSD affect neurotransmission

serotonin receptor agonist

how does caffeine affect neurotransmission

adenosine receptor antagonist

how does thc affect neurotransmission

CB1R agonist

how does nicotine affect neurotransmission

nAChR agonist

how does PCP affect neurotransmission

NMDAR (glutamate receptor) antagonist

alcohol at the receptor

increases the amount of Cl- that goes inside the cell

Alcohol at the synapse

GABA neuron binds to glutamate neuron which, more GABA decreases response in post synaptic cell

• alcohol in the synapse decreases the response more than just GABA alone would

What does dopamine do?

• controls movement

• part of the reward circuitry

• allows you to learn how to get a rewarding thing the first time

error learning ex.

go to a bush and find food (dopamine activated), go there again and find food (dopamine not activated), go there again and find bush no longer has food (dopamine activated)

what parts of the brain are part of the reward circuitry

• ventral tegmental area (produces dopamine)

• Nucleus Accumbens (reward center)

• Prefrontal Cortex

the rewarding and addicting properties of amphetamines rely on its ability to…

act as a substrate for these transporters and ultimately increase extracellular levels of monoamines (DA, NE, and 5HT)

action card; go read slide 17, idk how to put that in a flashcard wtf

kys

what are examples of other amphetamines

adderall, ritalin, dexedrine

amphetamines characteristics

• at correct doses, beneficial for those with ADD and ADHD

• act typically through increasing activity in the prefrontal cortex

• important for attention processes and cognition, such as working memory

drug addiction

a biological disorder in which, after a period of recreational use, a subset of individuals develops compulsive use that does not stop even in light of major negative consequences

substance dependence characteristics

• relapsing disorder

• compulson to seek and take the drug

• loss of control in limiting intake

• emergence of a negative emotional state when access to drug is prevented

addiction cycle transition from impulsive to compulsive

begins as pleasure/relief/gratification, then anxiety and stress occurs when not on the drug, so more of the drug is consumed to stop the negative effects

impulse control disorders are more closely related to what reinforcement

positive (pleasure/gratification)

compulsive disorders are more closely related to what reinforcement

negative reinforcement (relief of anxiety or stress)

major hypothesis of drug abuse

increased dopaminergic signaling from the midbrain ventral tegmental area (VTA) to the nucleus accumbens (NAc) is the initial common action of all addictive drugs

why does drug abuse happen

receptors become downregulated in response to excessive dopamine, so normal things no longer become enjoyable, meaning the drug is the only thing that works for pleasure

• receptors will then downgrade, so tolerance builds and MORE drug is needed

what does long term drug abuse lead to

reduction in activity and metabolism in the brain

what does brain do when it senses there is too much chemical

ex. when brain senses that for 10 receptors there are 100’s of dopamine NT’s, brain will downgrade receptors to compensate for huge influx (so same effect can occur as compared to when it had 10 for 10)

drug abusers “need”

once receptors are downregulated, you need the drug in order to maintain normal function, natural brain state is not enough to sustain activity

drugs that affect the nervous system primarily modulate….

chemical synaptic transmission

drugs are selective for…

different types of receptors and transporters

the brain circuit and type of neurotransmitter involved will determine…

how the drug affects overall brain function and ultimately behavior