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Transcript
Neurotransmitters
• Many Neurotransmitters (NT) exist:
-
Dopamine
Adrenaline
Serotonin
Acetylcholine
• Drugs can either:
– Increase the effect of certain neurotransmitter (agonist)
– Decrease the effect of certain neurotransmitter (antagonist)
Acetylcholine
curare
Belladonna
(atropine)
Synapse
Receptors for Acetylcholine
Cholinergic neurons
(release Acetylcholine)
Nicotine: Stimulates
Nicotinic receptors
- Muscarinic
- Nicotinic
Curare: Blocks nicotinic receptors
1. produce
2. pack
3. release
4. Bind
5. Post-synaptic changes
BOTOX
Ach-E
Atropine: Blocks muscarinic receptors
6.B Destroy
Pre-synaptic
Neuron
(axon)
Alzheimer’s treatment
Inhibits Ach-E
Post-synaptic
neuron
(dendrite)
Acetylcholine (Ach)
• Important for:
–
–
–
–
–
Muscle
myasthenia gravis (Antagonist, blocker)
Vigilance Nicotine mimics Ach effect in brain (Agonist)
Memory
Anti-cholinesterase drugs for Alzheimer’s disease (Agonist)
Learning Anticholinergic drugs (to prevent vomit) (Antagonist)
Autonomic Nervous System
dopamine
Dopaminergic neurons
Receptors for dopamine
- D1, D2, D4
(release dopamine)
D2
L-Dopa
Antipsychotic drugs for schizophrenia
Blocks D2 receptors
Precursor dopamine
pack
D2
release
Bind
Recycle
Pre-synaptic
Neuron
(axon)
Cocaine, amphetamine,
Methylphenidate (ritalin)
Makes dopamine transporter
work in reverse
Post-synaptic changes
D1
Post-synaptic
neuron
(dendrite)
Dopamine (DA)
• Important in:
– Movement control
– Schizophrenia (?)
– ADHD
– Drug addiction
•
•
death of dopaminergic cells in Parkinson’s disease
anti-psychotic drugs (antagonists)
metylphenidate (ritalin)
amphetamine, cocaine (agonist)
Schizophrenia treatment causes motor problems (as in parkinson’s)
Parkinson’s treatment causes hallucinations (as in schizophrenia)
Dopamine
The
Reward
System:
Dopamine
Activities of survival (sex, feed)
activate the reward system
Drugs of abuse similarly
activate the reward system
Electrical stimulation of the
reward system is also addictive
Electrical intracranial self-stimulation
stimulation
Olds & Milner (1954)
n. accumbens
The mind is its own place, and in itself, can make
heaven of Hell, and a hell of Heaven.
dopamine
(Satan, in John Milton’s Paradise Lost, book 1, ll. 254–5)
Quoted by R. Cardinal
VTA
Dopamine is released:
during sexual behavior
but also
in anticipation of sex (watching porn)
while eating yummy food
but also
in anticipation of food (picture)
but also
when seeing cocaine context
when doing cocaine
Craving:
– In rats, one injection activates dopaminergic neurons in
reward system of the abstinent rat (‘the first one is free’),
causing craving and relapse
Relapse
– Stressful stimuli increases animal’s susceptibility to relapse
Noradrenaline & Adrenaline
Oh no!
my
sympathetic
nervous
system is
overactive
again!
Serotonin (5-HT)
• Important in:
– Depression
• Receptors:
– Way too many!
• Drugs:
– Fluoxetine (prozac): inhibitor of reuptake (recycle) (SSRI)
– LSD: agonist of 5-HT2A
– Ectasy: agonist for serotonin and agonist for noradrenaline
GABA
• Is the most pervasive inhibitory NT in the brain
• Drugs:
– Benzodiazepines (valium): GABA Agonist
•
•
•
•
reduces anxiety,
promotes sleep,
anti-convulsant,
muscle relaxant
– Alcohol: GABA agonist
• Don’t drink while taking this medication
Alcohol
• Alcohol acts on three systems:
– Dopamine:
• causes euphoria,
• Addictive power
– GABA:
• reduces anxiety (at low levels)
• Sedative (at higher levels)
– Glutamate (NMDA):
• memory impairment
Tolerance
a decreased response due to frequent use.
• Metabolic tolerance: faster metabolism of the drug.This is
a pharmacokinetic mechanism (e.g., alcohol metabolization by
hepatic enzimes)
• Cellular-adaptive tolerance: down-regulation of receptors
(a pharmacodynamic mechanism)
Before drug
After Drug
Ways to administer a drug (& time to reach blood)