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 ethanol effects 2. Effects of ethanol on the nervous system

3 Alcohol Structure C O Methanol C C O Ethanol C C C O Propanol

4 Alcohol Structure C O Methanol Ingestion blindness C C O Ethanol TE alcohol C C C O Propanol Most t other alcohols l are highly hl toxic to the body

5 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)

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

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

8 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, Ca2) Enzymes Receptors Signals

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

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

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

12 Why Does Whiskey Burn?

13 Why Does Whiskey Burn? TRPv1 (Vanillin1) receptor (mouth, throat)

14 Why Does Whiskey Burn? eat, capsaicin

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

16 Why Do People Drink Alcohol?

17 Why Do People Drink Alcohol? Euphoria/Mood elevation Increase social confidence Anti-anxiety ( to relax ) Aphrodesiac Escape from problems To fit in with friends/family

18 Why Do People Drink Alcohol? Euphoria/Mood elevation Increase social confidence Anti-anxiety ( to relax ) Aphrodesiac Escape from problems To fit in with friends/family Because of great advertising?

19 Why Do People Drink Alcohol? Because of great advertising?

20 Why Do People Drink Too Much?

21 Why Do People Drink Too Much?

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23 This happens a LOT but why?

24 Why Do People Drink Too Much? Ethanol affects synapses Neuron signals and networks ( x 100 billion!)

25 Why Do People Drink Too Much? Ethanol affects synapses Neuron signals and networks ( x 100 billion!) Synapses, Neurotransmitters and Receptors

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

27 GABA Glut _ Glut Glut GABA _ Well-documented pharmacological effects of ethanol include stimulation of GABA signaling and inhibition of glutamate signaling. As the dose goes up, your intelligence goes down

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30 Mood/Pleasure GABA _ Glut Glut Glut GABA _ Serotonin Dopamine Other Neurotransmitters: Ethanol stimulates Other Neurotransmitters: Ethanol stimulates brain reward centers in a specific way.

31 Mood/Pleasure GABA _ Glut Glut Glut GABA _ Serotonin Dopamine.which can explain why:.which can explain why: Short-term: Drinking leads to more drinking Chronically: Addiction Both related to Rising Phase Effect

32 Rising Phase Effect Conten Elevated Dopamine: Reward/Euphoria Moderate Dose and Rate Bl lood Al lcohol Depressed Dopamine: Craving/Dependence Increasing Dose/Side Effects Moderate Dose/Effects Time

33 Rising Phase Effect Bl lood Al lcohol Conten Binge Drinking Increasing Dose/Side Effects Moderate Dose/Effects Time

34 Rising Phase Effect Conten Bl lood Al lcohol Binge Drinking Optimized Drinking Increasing Dose/Side Effects Moderate Dose/Effects Time

35 If drinking a little makes you happy, does drinking a lot make you really, REALLY happy? y, ppy (or depressed, or angry or horny?)

36 GABA Glut _ Glut Glut GABA _ Global depression model explaining situational dependence of alcohol s effect on mood and behavior: ALCOOL MYOPIA

37 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.

38 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.

39 Alcohol, Anxiety, and Public Speaking Alcohol drinks Volunteer subjects invited it 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

40 Alcohol, Anxiety, and Public Speaking

41 Myopia can boost your self-esteem! from: The Onion

42 ow Does Alcohol Affect Memory?

43 Short-Term Memory ( Working memory ) (RAM) LTP Long-Term Memory ( Learning ) (ard-drive)

44 Short-Term Memory LTP Long-Term Memory REM SLEEP RECENT LEARNING RESEARC

45 GABA Glut _ Glut Glut GABA _ Adenosine Alcohol affects neurotransmitters in a way that DOES make you go to sleep but..

46 but it is actually more like surgical anesthesia

47 and may seem hilarious to your friends

48 ..but

49 Short-Term Memory LTP Long-Term Memory REM SLEEP 1. ETANOL BLOCKS REM SLEEP

50 2. ETANOL INIBITS LTP Long-term potentiation at glutamate synapses is a cellular correlate of memory formation Even at moderate doses alcohol begins to inhibit LTP.

51 Memory Inhibition of memory formation GABA _ Glut Glut Glut GABA _ Impaired long-term memory formation: p g y After a single drink, LTP is reduced 30% At BAC of 0.2%, LTP is reduced 80% Total amnesia/blackout can occur at higher levels

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

53 TE COLLEGE STUDENT S GRAND DELUSION Study from 5-11 pm Party from 11-2 am LTP Long-Term Memory REM SLEEP

54 Why Do Drunks Talk Loud, Fall Down, and Get the Bed Spins?

55 GABA Glut _ Glut Glut GABA _ Global neural depression inhibits motor outputs and sensory inputs

56 GABA _ Glut Glut Glut GABA _ What the? Motor Output t Sensory Inputs SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)

57 GABA _ Glut Glut Glut GABA _ Motor Output t 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) (Bed spins)

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59 Calling alcohol a Drug doesn t mean it is evil.

60 Calling alcohol a Drug doesn t mean it is evil. Prescription Illegal OTC Oxycontin Cocaine Tylenol Prozac Ecstasy Nyquil Valium TC Ipecac Penicillin eroin Aspirin What do all drugs (and alcohol) have in common? What do all drugs (and alcohol) have in common? 1. Sought-after effects 2. Unintended side-effects 3. The dose determines the effect/side-effect ratio

61 Calling alcohol a Drug doesn t mean it is evil. In moderate doses (<1-2 drinks/day), alcohol appears to cause no harm*, and much evidence suggests that it may have positive effects. *EXCEPT in those who are pregnant, under 21, or susceptible to alcoholism. li

62 AN ONEST ALCOOL AD