1. 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)

2. curareBelladonna (atropine) Acetylcholine

3. Synapse

4. Pre-synaptic Neuron (axon) Post-synaptic neuron (dendrite) 1. produce 2. pack 3. release 5. Post-synaptic changes BOTOX 6.B Destroy Ach-E Alzheimer’s treatment Inhibits Ach-E Nicotine: Stimulates Nicotinic receptors Curare: Blocks nicotinic receptors Atropine: Blocks muscarinic receptors Cholinergic neurons (release Acetylcholine) Receptors for Acetylcholine - Muscarinic - Nicotinic 4. Bind

5. 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

6. dopamine

7. Pre-synaptic Neuron (axon) Post-synaptic neuron (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 release Bind D2D2 D2D2 D1D1 Antipsychotic drugs for schizophrenia Blocks D2 receptors Precursor

8. 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)

9. The Reward System: Activities of survival (sex, feed) activate the reward system Drugs of abuse similarly activate the reward system Dopamine Electrical stimulation of the reward system is also addictive

10. 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 VTA n. accumbens stimulation dopamine

11. Dopamine is released: in anticipation of food (picture) when seeing cocaine context during sexual behaviorin anticipation of sex (watching porn) when doing cocaine while eating yummy food but also

12. 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

13. Noradrenaline & Adrenaline Oh no! my sympathetic nervous system is overactive again!

14. Serotonin (5-HT) Important in: –Depression Receptors: –Way too many! Drugs: –Fluoxetine (prozac): inhibitor of reuptake (recycle) (SSRI) –LSD: agonist of 5-HT 2A –Ectasy: agonist for serotonin and agonist for noradrenaline

15. 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

16. 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

17. 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

18. Ways to administer a drug (& time to reach blood)