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Neurotransmitters

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).

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Neurotransmitters

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  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. Acetylcholine curare Belladonna (atropine)

  3. Synapse

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

  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. Receptors for dopamine • D1, D2, D4 Antipsychotic drugs for schizophrenia Blocks D2 receptors pack release Recycle Dopaminergic neurons (release dopamine) D2 L-Dopa Precursor dopamine D2 Post-synaptic changes Bind D1 Cocaine, amphetamine, Methylphenidate (ritalin) Makes dopamine transporter work in reverse Pre-synaptic Neuron (axon) Post-synaptic neuron (dendrite)

  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. TheReward System: Dopamine 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

  10. Electrical intracranial self-stimulation Olds & Milner (1954) stimulation n. accumbens 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 dopamine

  11. during sexual behavior in anticipation of sex(watching porn) while eating yummy food • in anticipation of food (picture) when doing cocaine when seeing cocaine context Dopamine is released: but also but also 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. Oh no! my sympathetic nervous system is overactive again! Noradrenaline & Adrenaline

  14. 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

  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. Tolerancea 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)

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