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

dopamine

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)