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Sex, Drugs, and the Brain. A chemical journey through pain and pleasure. Evolution of the Limbic System. Africanus had a brain about 1/3 the size of our modern brain. Africanus was primarily instinctive in behavior. Africanus was not capable of language.

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Sex, Drugs, and the Brain

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Sex drugs and the brain l.jpg

Sex, Drugs, and the Brain

A chemical journey through pain and pleasure


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Evolution of the Limbic System

Africanus had a brain about 1/3 the size of our modern brain

Africanus was primarily instinctive in behavior

Africanus was not capable of language

Africanus had practically no prefrontal cortex and was probably not capable of weighing options

Yet, deep inside our brain is the brain of Africanus. Our limbic system has not changed greatly in 2 million years.

Australophithecus Africanus


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The Limbic System

Ventricle


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The Neuron


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Photographs of Real Neurons

dendrite

axon


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The Synapse

terminal button of neuron 1

presynaptic neuron

0.2 mm

dendrite of neuron 2

postsynaptic neuron


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Neurons Communicate through Chemical Messengers

neurotransmitter

neurotransmitter receptor


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Monoamine Neurotransmitters

  • Common Features

  • phenol or catachol ring

  • 2-carbon aliphatic amine chain

  • Destroyed by MAO

dopamine

norepinephrine

serotonin

adrenaline


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Biosynthesis of Dopamine and Norepinephrine

tyrosine

L-DOPA

norepinephrine

dopamine


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Neurotransmitters are Carefully Regulated

*

Simultaneous formation and destruction affords careful regulation of neurotransmitter levels in brain

biosynthesis

*

*

MAO

3,4-dihydroxyphenylacetic acid


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Dopamine Pathways

The mesolimbic pathway aka the “pleasure center”

The mesolimbic pathway is your reward system for behavior that needs to be reinforced (eating, seeking warmth or shelter, sex, winning a fight, etc.)

septum


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Methamphetamine Action


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Cocaine Action


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Heroin Action


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Septum is Focal Point for Pleasure

Dr. Robert Heath

Dr. James Olds

Stimulation of the septum produces intense pleasure


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Molecular Design by Analogues

azobenzene


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Natural Neurotransmitter Analogues

Psilocybe Mexacana

cacao

nutmeg

Peyote cactus

Yopo tree

Ergot fungus


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Naturally Occurring Dopamine Analogues

mescaline (from Peyote cactus)

dopamine (from brain)

cathanone (from Kat)

phenylethylamine (from chocolate)

ephedrine (from Ephedra)


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Synthetic Dopamine Analogues

amphetamine (goofballs)

methamphetamine (speed, crystal meth, crank)

methylenedioxoamphetamine (MDA)

methylenedioxomethamphetamine (MDMA, XTC, love drug, E)


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Natural Serotonin Analogues

Yopo

from a Peruvian tree

psilocybin

from Psilocybe Mexicana (Magic Mushroom)

serotonin

from brain

lysergic acid

psilocin

from Ergot fungus

from Magic Mushroom


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Synthetic Serotonin Analogues

diethyltryptamine(DET)

lysergic acid diethylamide(LSD, acid)

dimethyltryptamine(DMT)


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Pioneers of Neurotransmitter Analogues

Dr. Albert Hoffman

Dr. Alexander Shulgin


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Harvard University Psilocybin Research Project

Dr. Timothy Leary

Aldous Huxley

Prof. Richard Alpert

Two year study of the effects of psilocybin analogs on the scholarly creativity of students


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Molecular Design of Dopamine Antagonist by QSAR

Used with permission from Wyeth-Ayerst Laboratories, 2005


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Practical Uses of Neurotransmitter Analogues

L-DOPA (Parkinson’s)

Tigan (antischizophrenic)

Clozapine (antipsychotic)

Haloperidol (antipsychotic)


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The Remote-Controlled Cockroach

This cockroach has an electrode array implanted in its brain, and can be steered by radio control

From Northwestern University, Chicago, IL


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Sex and Love are Different

nucleus accumbens

Think about sex

Think about love

prefrontal cortex


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Addicted to Love (quite literally!)

Dr. Helen Fisher Rutgers University

Dr. Sue Carter University of Illinois

Dr. Karen Bales University of California

These researchers study the role of neuropeptides in pair-bonding (romantic love)


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What We Learned from the Prairie Vole

Prairie vole is a monogamous species. That is, it finds a mate and stays together for life

Its close cousin, the Montane vole, is non-monogamous. It never mates with the same partner twice

Yet, the Prairie vole and Montane vole have essentially the same brain. So, what causes this dramatic behavioral difference?


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Two Important Neuropeptides

different by only two amino acid residues


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Effects of Oxytocin on Behavior

Injecting oxytocin into a Montane vole will cause it to temporarily act like a Prairie vole

Injecting a Prairie vole with an oxytocin blocker will cause it to temporarily act like a Montane vole

In humans, oxytocin levels increase when we are in love, increase when we simply touch our pets, and, in women, increase dramatically just after childbirth

Hypothesis: Could oxytocin be the molecule of love?


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Might as Well Face it, You’re Addicted to Love … Robert Palmer, 1995

Love

high endorphin levels

High serotonin levels

Low dopamine

Low testosterone

Heartbreak

Low endorphin levels

Sudden drop in serotonin

Low dopamine

Low testosterone

Drug addiction

High endorphin levels

High serotonin levels

Low dopamine

Low testosterone

Drug withdrawal

Low endorphin levels

Sudden drop in serotonin

Low dopamine

Low testosterone


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The Chemistry of “Chemistry”

A play in three acts


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Meet the Players

norepinephrine

aka Mr. Excitement

oxytocinaka Cuddles

dopamine

aka Mr. Desire

vasopressinaka Mother Superior

serotonin

aka Mr. Happy

testosteroneaka Sarge


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Act 1: Strangers in the Night

Scene 1: Testosterone elevates in the blood, signals the body to physically respond, and influences the decision making areas of the brain to “go for it”

Scene 2: Sensory information enters the brainstem triggering the release of dopamine in the ventral tegmentum

Scene 3: The ventral tegmentum fires a series of signals into the limbic system via the mesolimbic dopamine pathway

Scene 4: Norepinephrine elevates in the limbic system signaling the onset of pleasure. The hypothalamus and pituitary convert norepinephrine into adrenaline triggering a “fight or flight” response, resulting in emotional excitement


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The Mesolimbic Dopamine Pathway

Scene 5: dopamine signals enter the septum, the main focal point of the “pleasure center”

Scene 6: dopamine signals reach the nucleus accumbens, reinforcing this behavior

Scene 7: dopamine signals make it to the prefrontal cortex, the decision making headquarters

Scene 8: the prefrontal cortex now makes a series of decisions, weighing options and consequences, and simultaneously stimulates the septum, nucleus accumbens, and amygdala


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Act 2: Now it gets Complicated

Enter stage left: Oxytocin and Vasopressin

As our lovers become increasingly enchanted with each others charms, the hypothalamus perks up and manufactures two neuropeptides, oxytocin (aka cuddles) and vasopressin (aka mother superior), and releases both of them into the cerebrospinal fluid. There they have full access to all the organs of the limbic system

Scene 9: Oxytocin binds to hippocampus, allowing the lovers to remember each other

Scene 10: Vasopressin binds to septum, dulling reward, and binds to amygdala causing warning signals, fear, and inhibition of attachment

Scene 11: Oxytocin binds to nucleus accumbens, causing memory of “pleasure” to associate with this particular person


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Pair-bond? Yes or no?

Scene 12: The prefrontal cortex takes all sensory inputs, inputs from hippocampus, and inputs from memory, and goes into high gear to make decisions. These decisions are conveyed back to the limbic system as signals to the cingulate (“happy” vs. “unhappy”), amygdala (fear or threat of impending loss), septum (pleasure), and nucleus accumbens (habituation).

Scene 13: In the meantime, “cuddles” and “mother superior” are battling it out. If cuddles wins, you’re in love. If mother superior wins, you’re just having fun.

Scene 14: Oxytocin (cuddles) wins – you’re in love!

and all this happens in just 4 minutes


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The Script

The scene takes place in the limbic system of a young man sitting with his date at the Underground Pub at York University on a Saturday night. There is no shortage of young women dancing a few feet away.

Testosterone: Look at that one. No, look at that one. No, look at that one.

Dopamine: Boy o boy o boy, is this gonna be fun or what?

Vasopressin: Don’t look at other girls, you’ll die

Testosterone: What’s a matter with you, yella? Reach over and hold her hand

Vasopressin: Don’t touch her hand, you’ll die

Oxytocin: Oh let’s hold hands all night and stare in her eyes, and hug

Testosterone: Hug, shmug! What a waste of time. Go for the gusto soldier!

Vasopressin: Stop! Do that and you’ll die

Testosterone: Oh, don’t listen to that you’ll do nothing. Go for the gusto soldier!

Oxytocin: I need a hug

Dopamine: Boy o boy, is this gonna be fun or what?

Vasopressin: If you listen to Sarge, you’ll die


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Intermission

All seems good with our lovers, BUT …..

Something nasty is happening in our lovers’ brains!!

All this limbic activity is dropping serotonin level fast and hard

Exit Stage Right


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New Love is a Psychosis

Within days, serotonin drops to levels mimicking that found in patients with obsessive-compulsive disorder

When our lovers are separated they literally obsess over each other.


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Act 3: Oxytocin to the Rescue

Oxytocin acts as a serotonin reuptake inhibitor (naturally occurring Prozac). In about 6 months, serotonin is back to normal

Enter stage left - Serotonin


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THE END

DISCLAIMER: As serotonin levels build, physical attraction between our lovers wanes. High oxytocin levels also inhibit the action of vasopressin and testosterone, further diminishing excitement in the relationship. This begins at about 17 months. There is about a 50% chance the relationship will end in roughly 4 years.


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Acknowledgements

York University Department of Chemistry

Dr. Gillian Wu, Dean of Science and Engineering

Science Speakers Bureau

You


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Proximity of amygdala and nucleus accumbens

Nucleus accumbens

amygdala


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The Bonobo Chimpanzee

Dr. Susan Block

The Bonobo is a hominid and is our closest genetic relative sharing 99.7% of our genes


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Pheromones

DEET (alarm pheromone for ticks, fleas, mosquitoes)

Hamsters (sex attractant)

Cockroach (sex attractant)

Gypsy moth (male sex attractant)


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Truffles and Sex

  • Truffles have historically been used to “impress” a female date

  • Truffles are very expensive and are a sign of power and wealth

  • Consequently it had been assumed that the “power of the truffle” was due to it’s symbolism for wealth

  • HOWEVER …. It may be more complicated!


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Truffles and Pigs

Truffles are mushrooms that grow underground

Female pigs can smell truffles over 1 meter underground. Sometimes they dig so ferociously that they have to be physically restrained.


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Why do pigs like truffles so much?

HINT: They don’t eat them

1981 - Drs. Claus and Hoppen at the Technical University of Munich and Dr. Kong at the Lubeck School of Medicine independently found the active attractant in truffles

androstenol

Sows exposed to pure androstenol become uncontrollably “sex-crazed”


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Androstenol

  • Androstenol is an analogue of testosterone

  • Androstenol is produced in the testes of boars and transported to the salivary glands

  • Sows exhibit a pronounced Lordosis reflex when they smell the breath of a boar

  • Androstenol is also produced in the testes of humans and transferred to underarm sweat glands

Androstenol

testosterone

Could androstenol be a human sex pheromone?


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Obvious next experiment

Let female humans smell androstenol and see if they become uncontrollably sex-crazed

Dr. Michael Kirk-Smith, University of Birmingham (every male graduate student volunteered to conduct the experiment)

  • Women (who self-identified as straight) were shown pictures of men and asked to rate them on a scale from 1 to 10

  • Control group rated them at 6 (average)

  • Androstenol group rated them at 6 (average)

  • HOWEVER --- androstenol group rated photos of OTHER WOMEN at 8, as opposed to 5 for control group!

CONCLUSION: androstenol makes women more attractive to women


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So, is androstenol a real human sex pheromone?

Apparently not – social factors can override any pheromone control (if there is any)

But it’s sure being marketed like it is


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Women – don’t feel left out

The same company markets to you too


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Androstenol smells like musk

  • It has been known for centuries that perfumes and colognes that smell “musky” tend to be better received by the opposite sex

  • Women can smell exaltolide, an analogue of muskone, men cannot!

  • After inhaling exaltolide, women become more social

  • Exaltolide is currently used in almost all colognes for men

  • If a man is injected with estrogen, he can suddenly smell exaltolide!

Muskone (from Musk Deer)

Exaltolide (synthetic analogue)


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The Martha McClintock Story

  • Heard that women who live together get their periods together

  • Performed a study of 135 residents of a women’s dorm (8 to a room)

  • Found that by March all roommates had periods within 5 days of each other

  • Demonstrated for the first time the existence of a human pheromone

  • Published her work in Nature

Martha McClintock, age 19

Harvard University psychology major


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Essence of Genevieve

Dr. Mark Russel, Brain Behavior Research Institute, Sonoma State Hospital, California

  • read McClintock paper in Nature and became interested in identifying the pheromone

  • Had a lab assistant named Genevieve wear sterile cotton underarm pads for several days

  • Extracted the pads with alcohol and applied the extraction to upper lip of eight women

  • Found all 8 women’s periods synchronized to within 4 days in less than 2 months

  • Conclusion: pheromone is in underarm sweat


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Now she found another one

Took the breast pads (unwashed) of over 100 nursing women and extracted them with alcohol

Treated handkerchiefs with the alcohol solution and had other women wear the handkerchiefs close to their faces for several days

FINDINGS

The other women had a dramatic increase in sexual fantasies.

Breast “essence” from non-breastfeeding women had no effect.

No effect of any kind on men

Professor Martha McClintock

University of Chicago


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