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)

curareBelladonna (atropine) Acetylcholine

Synapse

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

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-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

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)

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

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

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

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-HT 2A –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)