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)
curare Belladonna (atropine)
Acetylcholine
Synapse
Pre-synapticNeuron(axon)
Post-synapticneuron
(dendrite)
1. produce 2. pack 3. release5. Post-synaptic changes
BOTOX
6.B Destroy
Ach-E
Alzheimer’s treatmentInhibits Ach-E
Nicotine: StimulatesNicotinic receptors
Curare: Blocks nicotinic receptors
Atropine: Blocks muscarinic receptors
Cholinergic neurons (release Acetylcholine)
Receptors for Acetylcholine- Muscarinic
- Nicotinic
4. Bind
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
Pre-synapticNeuron(axon)
Post-synapticneuron
(dendrite)
L-Dopa
Post-synaptic changes
Recycle
dopamine
Dopaminergic neurons (release dopamine)
Receptors for dopamine- D1, D2, D4
Cocaine, amphetamine,Methylphenidate (ritalin)
Makes dopamine transporter work in reverse
pack releaseBind
D2
D2
D1
Antipsychotic drugs for schizophreniaBlocks D2 receptors
Precursor
Dopamine (DA) • Important in:
– Movement control death of dopaminergic cells in Parkinson’s disease– Schizophrenia (?) anti-psychotic drugs (antagonists) – ADHD metylphenidate (ritalin)– Drug addiction amphetamine, cocaine (agonist)
• Schizophrenia treatment causes motor problems (as in parkinson’s)• Parkinson’s treatment causes hallucinations (as in schizophrenia)
TheReward
System:
Activities of survival (sex, feed) activate the reward system
Drugs of abuse similarly activate the reward system
Dopamine
Dopamine
Electrical stimulation of the reward system is also addictive
Electrical intracranial self-stimulation
Olds & Milner (1954)
The mind is its own place, and in itself, can make heaven of Hell, and a hell of Heaven.
(Satan, in John Milton’s Paradise Lost, book 1, ll. 254–5)Quoted by R. Cardinal
VTAn. accumbens
stimulation
dopamine
Dopamine is released:
in anticipation of food (picture)
when seeing cocaine context
during sexual behavior in anticipation of sex (watching porn)
when doing cocaine
while eating yummy food
but also
but also
but also
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)