Physiology of the World s Second-Most Popular Drug. Kevin T. Strang, PhD Department of Physiology

Transcription

1 Physiology of the World s Second-Most Popular Drug Kevin T. Strang, PhD Department of Physiology

2 1. Cellular mechanism of alcohol effects 2. Effects on the nervous system

3 I. Mechanism of Alcohol Effects

4 Alcohol Structure C O Methanol C C O Ethanol C C C O Propanol

5 Alcohol Structure C O Methanol Ingestion blindess C C O Ethanol TE alcohol C C C O Propanol Most other alcohols are highly toxic to the body

6 Ethanol Structure Clear, colorless liquid, miscible with 20 and Organics Carbon-ydrogen chains dissolve in lipids (hydrophobic) C C O This end interacts and dissolves in water (hydrophilic)

7 Basic Structure of Body Cells Our bodies are made of 75 trillion specialized cells with phospholipid membranes, and aqueous environments inside and out.

8 Basic Structure of Body Cells Cell membranes are essentially oily bubbles formed from a bilayer of phospholipid molecules

9 Basic Structure of Body Cells Proteins are the machinery that determine the function of different cell types; they re found floating free and within membranes Ion channels (Na+, K+, Ca+2) Enzymes Receptors Signals

10 Basic Structure of Body Cells Proteins are made of amino acid chains: 20 different amino acids have unique R groups: Some are hydrophilic Some are hydrophobic 3

11 Basic Structure of Body Cells Proteins are made of amino acid chains: The R -group sequence determines the complex folding and final shape of a protein.

12 Ethanol Interacts with Cell Proteins Ethanol s unique chemistry makes it a skeleton key that can interact with protein machinery of cells throughout the body. (hydrophobic) C C O (hydrophilic)

13 e.g., Ethanol can alter gating properties of many different types of ion channels

14 Why Does Whiskey Burn?

15 Why Does Whiskey Burn? Vanillin Receptor 1 (mouth, throat)

16 Why Does Whiskey Burn? eat, capsaicin.and Ethanol!

17 Why Does Whiskey Burn? eat, capsaicin.and Ethanol! OT!! Nerve signal to brain

18 Drug isn t a four-letter-word.

19 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin

20 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin What do all drugs (and ethanol) have in common?

21 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin What do all drugs (and ethanol) have in common? 1. Sought-after effects

22 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin What do all drugs (and ethanol) have in common? 1. Sought-after effects 2. Unintended side-effects

23 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin What do all drugs (and ethanol) have in common? 1. Sought-after effects 2. Unintended side-effects 3. The dose determines the effect/side-effect ratio

24 Drug isn t a four-letter-word. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin Alcohol is a pharmacological hand grenade. Stephen Braun--Buzz

25 Endocrine/ Reproductive Ethanol Affects All Body Systems Cardiovascular Gastrointestinal Urinary Today s Focus: Nervous System

26 Ethanol affects synapses Neuron signals and networks ( x 100 billion!) Synapses, Neurotransmitters and Receptors

27 Why was the drinking age raised from 18 to 21?

28 GABA _ Glut + + Glut + Glut GABA _ Normal cognition depends on a balance of excitatory and inhibitory synaptic activity: 50% of the brain s synapses use Glutamate 40% use GABA (gamma-amino-butyric acid)

29 GABA _ Glut Glut Glut GABA _ Well-documented pharmacological effects of ethanol include stimulation of GABA signaling and inhibition of glutamate signaling. Overall effects are dose and situation dependent.

30 Alcohol Myopia Can Explain Variable Neural Effects The basic idea: Ethanol globally suppresses cognition, reducing the mental focus of an individual to immediate internal thoughts or external stimuli.

31 Alcohol Myopia Can Explain Variable Neural Effects The basic idea: Ethanol globally suppresses cognition, reducing the mental focus of an individual to immediate internal thoughts or external stimuli. Example: Study demonstrating that ethanol is NOT a good anti-anxiety drug.

32 Alcohol, Anxiety, and Public Speaking Alcohol drinks Volunteer subjects invited to a party Placebo drinks In 15 minutes, you have to go on stage and give an impromptu speech: What I dislike most about my body and physical appearance ANXIETY ANXIETY Sit and think Easy slide sorting task Moderate difficulty slide sorting task Complicated slide sorting task

33 Alcohol, Anxiety, and Public Speaking

34 Myopia can also boost self-esteem! from: The Onion

35 Mood/Pleasure GABA _ Glut Glut Glut GABA _ Serotonin Dopamine Other Neurotransmitters: Ethanol stimulates brain reward centers.

36 Mood/Pleasure GABA _ Glut + + Glut + Glut GABA _ Serotonin Dopamine TIS EXPLAINS: Short-term: Drinking leads to more drinking Chronically: Addiction Both related to Rising Phase Effect

37 Rising Phase Effect Blood Alcohol Content Elevated Dopamine: Reward/Euphoria Moderate Dose and Rate Depressed Dopamine: Craving/Dependence Increasing Dose/Side Effects Moderate Dose/Effects Time

38 Rising Phase Effect Blood Alcohol Content Binge Drinking Increasing Dose/Side Effects Moderate Dose/Effects Time

39 Rising Phase Effect Blood Alcohol Content Binge Drinking Optimized Drinking Increasing Dose/Side Effects Moderate Dose/Effects Time

40 Memory GABA _ Glut + + Glut + Glut GABA _ OTER SIDE EFFECTS: Impaired memory formation (low doses!) Amnesia/Blackout (higher doses)

41 Memory GABA _ Glut + + Glut + Glut GABA _ OTER SIDE EFFECTS: The Onion, June 21, 2007 Impaired memory formation (low doses!)

42 WAT IS LEARNING? Short-Term Memory ( Working memory ) (RAM) Assimilation Long-Term Memory ( Learning ) (ard-drive)

43 Short-Term Memory + Long-Term Memory SLEEP NEW LEARNING RESEARC

44 WAT IS LEARNING? ETANOL Short-Term Memory Long-Term Memory

45 WAT IS LEARNING? ETANOL Short-Term Memory + Long-Term Memory SLEEP TE GRAND DELUSION

46 GABA _ Glut + + Glut + Glut GABA _ Motor Output Sensory Inputs SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)

47 GABA _ Glut + + Glut + Glut GABA _ Motor Output Sensory Inputs SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats) 2. 8 th Cranial Nerve especially sensitive ( Dude, turn it up ) (Field sobriety test)

48 GI SYSTEM TO TE RESCUE

49 Vomit: to puke, purge, barf, hurl, yak, chunky exhale, yawn in Technicolor, worship the porcelain god, talk to Ralph on the big white phone Normally: stretch stomach bacteriotoxin wall brainstem vomit excess acid receptors

50 stretch stomach bacteriotoxin wall brainstem excess acid receptors indirect direct Side Effect: igh ethanol concentrations cause vomiting

51 BEER ADVERTISING

52 BEER AD DISCLAIMER

53 QUESTIONS?