Ethanol

The Physiology Behind the World’s Second Most Popular Drug

Kevin T. Strang, PhDDepartment of Physiology

Alcohol Structure

CH

HH OH

CH

HH OH

CH

HH OH

CH

H

CH

HCH

H

Methanol

Ethanol

Propanol

Alcohol Structure

C

H

H

H OH

CH

HH OH

C

H

H

H OH

CH

H

C

H

H

C

H

H

Methanol

Ethanol

Propanol

THE alcohol

Ingestion blindess

Most “other” alcohols are highlytoxic to the body

CH

HH OHC

H

H

Ethanol Structure

•Clear, colorless liquid, miscible with H20 and organics

This end interacts anddissolves in water(hydrophilic)

Carbon-Hydrogen chainsdissolve in lipids(hydrophobic)

Cell membranes are essentially oily bubbles formedfrom a bilayer of phospholipid molecules

Basic Structure of Body Cells

Proteins are the machinery that determine thefunction of different cell types; they’re foundfloating free and within membranes

Ion channels(Na+, K+, Ca+2)

Enzymes

Receptors

Signals

Basic Structure of Body Cells

Proteins are made of amino acid chains:

Different amino acids haveunique “R” groups:

• Some are hydrophilic• Some are hydrophobic

3

Basic Structure of Body Cells

Ethanol’s unique chemistry allows it to interact with protein machinery of cellsthroughout the body.

CH

HH OHC

H

H(hydrophilic)

(hydrophobic)

Ethanol Interacts with Cell Proteins

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

Why Does Whiskey “Burn”?

Why Does Whiskey “Burn”?

“Vanillin Receptor 1” (mouth, throat)

Why Does Whiskey “Burn”?

Heat, capsaicin….

Why Does Whiskey “Burn”?

Heat, capsaicin….and ethanol!

Nerve signalto brain

“HOT!!”

Ethanol Affects All Body Systems

CardiovascularGastrointestinal Urinary

Endocrine/Reproductive

Today’s Focus:Nervous System

Mood elevationMild euphoriaReduced social inhibitionsAnti-anxiety

Why Do People Drink ?

Mood elevationMild euphoriaReduced social inhibitionsAnti-anxiety

But the effects aren’t as predictable as other drugsand there are side effects……

Why Do People Drink ?

Ethanol affects synapses

Neuron signalsand networks

( x 100 billion!)

Synapses, Neurotransmittersand Receptors

Glut Glut

Glut

Normal cognition depends on a balance of excitatoryand inhibitory synaptic activity:

50% of the brain’s synapses use Glutamate 40% use GABA (gamma-amino-butyric acid)

+ +

+

GABAGABA

_

_

Glut Glut

Glut+ +

+

GABAGABA

_

_

Well-documented pharmacological effects of ethanolinclude stimulation of GABA signaling and inhibitionof glutamate signaling.

Dose-dependent decline in cognitive ability……

Glut Glut

Glut+ +

+

GABAGABA

_

_

Global neural depression inhibits motor outputsand sensory inputs……

Glut Glut

Glut

SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)

+ +

+

GABAGABA

_

_

MotorOutput

SensoryInputs

Glut Glut

Glut

SIDE EFFECT: Depression of motor output and sensory input 1. Loss of coordination (see drunk driving stats)2. 8th Cranial Nerve especially sensitive

(“Dude, turn it up!”) (Field sobriety test) (Bed spins)

+ +

+

GABAGABA

_

_

MotorOutput

SensoryInputs

How Does Alcohol Affect Memory?

Long-term potentiationat glutamate synapsesis a cellular correlateof memory formation

How Does Alcohol Affect Memory?

Long-term potentiationat glutamate synapsesis a cellular correlateof memory formation

Even at moderate dosesalcohol begins to inhibit LTP….

How Does Alcohol Affect Memory?

Short-TermMemory(“Working

memory”)(RAM)

Long-TermMemory(“Learning”)(Hard-drive)

Assimilation

ALCOHOL AND LEARNING

Short-TermMemory

Long-TermMemory

NEW LEARNING RESEARCH

SLEEP

+

WHAT IS LEARNING?

Short-TermMemory

Long-TermMemory

ETHANOL

WHAT IS LEARNING?

Short-TermMemory

Long-TermMemory

THE GRAND DELUSION…

SLEEP

+

ETHANOL

Glut Glut

Glut

Impaired long-term memory formation: 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

+ +

+

GABAGABA

_

_

Memory

Inhibition of memory formation

What Makes a Mean Drunk Mean?(or happy or horny or depressed?)

Glut Glut

Glut+ +

+

GABAGABA

_

_

Well-documented pharmacological effects of ethanolinclude stimulation of GABA signaling and inhibitionof glutamate signaling.

Overall MOOD effects are dose and situation dependent.

“Alcohol Myopia” Can Explain Variable Neural Effects

The basic idea:

Ethanol globally suppresses cognition, reducingthe mental focus of an individual to immediateinternal thoughts or external stimuli.

“Alcohol Myopia” Can Explain Variable Neural Effects

The basic idea:

Ethanol globally suppresses cognition, reducingthe mental focus of an individual to immediateinternal thoughts or external stimuli.

Example: Study demonstrating that ethanol isNOT a good anti-anxiety drug….

Alcohol, Anxiety, and Public Speaking

Volunteer subjectsinvited to a party

“In 15 minutes, you have to go on stage and give an impromptu speech:”What I dislike most about my body and physical appearance

Alcohol drinks Placebo drinks

Sit and think

Easy slidesorting task

Moderate difficulty slide sorting task

Complicated slidesorting task

ANXIETY ANXIETY

Alcohol, Anxiety, and Public Speaking

Myopia CAN boost self-esteem!

from:The Onion

Why is it So Hard to Have Just One?

Glut Glut

Glut+ +

+

GABAGABA

_

_

Mood/Pleasure

SerotoninDopamine

Other Neurotransmitters: Ethanol stimulatesbrain “reward” centers.

Glut Glut

Glut

THIS EXPLAINS:Short-term: Drinking leads to more drinking Chronically: AddictionBoth related to “Rising Phase Effect”

+ +

+

GABAGABA

_

_

Mood/Pleasure

SerotoninDopamine

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Elevated Dopamine:Reward/Euphoria

Depressed Dopamine:Craving/Dependence

Moderate Dose and Rate

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Binge Drinking

Rising Phase Effect

Time

Blo

od A

lcoh

ol C

onte

nt

Increasing Dose/Side Effects

Moderate Dose/Effects

Binge DrinkingOptimized Drinking

WHY DO BEER AND BRATS MAKE A GREAT TEAM?

WHY DO BEER AND BRATS MAKE A GREAT TEAM?

Fatty foods are best at delaying the emptying of the stomach (enterogastric reflex)

Reduces the rate of rise of blood alcohol 3-fold!

Always eat before/during alcohol consumption!

How Does the GI System Save Lives?

Normally:

stretch stomachbacteriotoxin wall brainstem vomitexcess acid receptors

How Does the GI System Save Lives?

stretch stomachbacteriotoxin wall brainstemexcess acid receptors

High ethanol concentrations stimulate stomach wall receptors 2 ways:

direct

indirect

How Does the GI System Save Lives?

Prescription Illegal OTCOxycontin Cocaine TylenolProzac Ecstasy NyquilValium THC IpecacPenicillin Heroin Aspirin

What do all “drugs” (and ethanol) have in common?1. Sought-after effects2. Unintended side-effects3. The dose determines the effect/side-effect ratio

“Drug” isn’t a four-letter-word….

Think of alcohol as a “drug”

In moderate doses (<1-2 drinks/day),alcohol appears to cause no harm*,and much evidence suggests that itmay have positive effects.

*EXCEPT in those who are under 21, pregnant, or susceptibleto alcoholism.

Moderate doses seem to be good for you…..