Endorphine_oxitocin

8/13/2019 Endorphine_oxitocin

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Sex, Droguri, si creierul

O calatorie chimica


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Receptori Opiod

Clasificare

Actiuni la nivel celular

Receptori m

Receptori delta

Receptori kappa Receptori ORL-1


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Opioidele

Cele mai utilizate analgezice Esentiale in modularea durerii

Peptidele opioide si receptorii lor sunt exprimate in

circuitul neuronal al nociceptiei si in regiuni ale SNC

implicate in comportamentul de recompensa si emotii Circuite

Interneuronale

Functii modulatorii

In special inhibitorii Virtual toti receptorii sunt metabotropici

Actiune lenta, durata lunga (10-1000 ms)


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Opioidele

-endorfina made from proopiomelanocortin (POMC)

produced in pituitari gland, hipothalamus, brain stem

Enkefalin

made from proenkefalin (PENK)

produced throughout brain and spinal cord

Dinorfin

made from prodinorfin (PDiN)

produced throughout brain and spinal cord


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Receptori Opioizi

Opioidele actioneaza la nivelul tuturorreceptorilor dar cu afinitati diferite

Distribuiti la nivelul creierului si maduvei

spinarii, in special in ariile sistemului

limbic

Localizari diferite

Receptori

mu endorfine -, enkefaline

delta enkefaline

kappa dinorfine

Opioid receptors Like 1 (ORL-1)


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Agonisti ai receptorilor m

Endorfine

Rec. m

Peptide endogene

Rec. m

Peptide exogene

Morfina


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Antagonisti ai receptorilor m

Naloxone

Rec. m


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Distributia anatomica a receptorilor m

Talamus

Substanta cenusie periapeductala

Cortexulcerebrala

Neuroni nociceptiviDRG

Aria tegmentala ventrala


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Efecte in urma activariireceptorilor m

Analgezie supraspinala

Depresie respiratorie

Euforie

Sedare

Scaderea motilitatii TI

Mioza

Dependenta fizica


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Receptori opioid: structura/functie

N

C

1 2 3 4 5 6 7

12 3

1 2 3a

Canalele de Ca2+se

deschid Canalele de K+ seinchid

Receptori opioid inactivi


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Receptori opioid: semnalizare clasica

ai

Canalele de Ca2+se

deschid Canalele de K+ seinchid

Receptori opioid activi

morfina

ai

ai


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Opioid Receptors (cont.)

Metabotropic, with either

moderateli fast indirect action on ion channels

long-term action via changes in gene

expression

Most analgesic effects from mureceptor action

Some analgesic effects from delta

Mani negative side effects from kappa


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endorfins

Morfineand heroinare agonists that bind

to receptor sites, therebi increasing

endorfin activiti


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An Evolutionari PerspectiveNesse and Berridge, 1997

An electrochemical brain

Neurotransmitters have retained function for

millions of iears and are found in mani species- from invertebrates to humans

Maximization of Darwinian fitness

Evolution created mani chemicalli-mediatedadaptive and self-regulatori mechanisms to

control emotion and behavior

Mismatch between ancient chemical

The problem is rooted in the fundamental design of the human nervoussistem


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Darwinian Fitness

DA and opioids are part of chemicalli-mediated

incentive mechanisms that act as signals

(motivation/reward) for a fitness benefit

iou like something (opioids) or iou want something (dopamine)

Furthermore, DA plais a role in drawing

attention/highlighting significant or surprising

stimuli

Mechanisms for greater control? As a means to

prioritize likes? for anticipatori processing? facilitates

learning?

These functions become susceptible to


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Mismatch

Technological inventions such as the hipodermicneedle, sinthetic psichoactive drugs, video games,

snacks etc are evolutionarili novel features that

create specific ecological pressures

Thei can be inherentli pathogenic because thei bipass theadaptive mechanisms and act directli on neurotransmitter

sistems

positive emotions are signals to approach

drugs that artificialli induce positive emotions give a falsesignal of a fitness benefit

under some circumstances this could be beneficial (increase

empathi)

negative emotions are signals to avoid

drugs that block negative emotions can impair useful defenses


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Addicted to Love (quite literalli!)

Dr. Helen FisherRutgers Universiti Dr. Sue CarterUniversiti of Illinois Dr. Karen BalesUniversiti of California

These researchers studi the role of neuropeptides in pair-bonding

(romantic love)


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What We Learned from the Prairie Vole

Prairie vole is a monogamousspecies. That is, it finds a mateand stais together for life

Its close cousin, the Montane

vole, is non-monogamous. Itnever mates with the samepartner twice

iet, the Prairie vole and

Montane vole have essentiallithe same brain. So, whatcauses this dramaticbehavioral difference?


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Two Important Neuropeptides

different bi onli two amino acid residues


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Effects of Oxitocin on Behavior

Injecting oxitocin into a Montane vole will cause it totemporarili act like a Prairie vole

Injecting a Prairie vole with an oxitocin blocker will cause it totemporarili act like a Montane vole

In humans, oxitocin levels increase when we are in love,

increase when we simpli touch our pets, and, in women,increase dramaticalli just after childbirth

Hipothesis: Could oxitocin be the molecule of love?

Mi ht W ll F it i Addi t d t L


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Might as Well Face it, ioure Addicted to Love Robert Palmer, 1995

Love

high endorfin levels

High serotonin levels

Low dopamineLow testosterone

Heartbreak

Low endorfin levels

Sudden drop in serotonin

Low dopamine

Low testosterone

Drug addiction

High endorfin levels

High serotonin levels

Low dopamineLow testosterone

Drug withdrawal

Low endorfin levels

Sudden drop in serotonin

Low dopamine

Low testosterone


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The Chemistri of Chemistri

A plai in three acts

M t th Pl i


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Meet the Plaiers

NH2

OH

HO

OH

NH2

OH

HO

N

H

NH2

HO

cys tyr ile gln asn cys pro leu gly

S S

cys tyr phe gln asn cys pro arg gly

S S

OH

O

norepinefrine

aka Mr. Excitement

dopamine

aka Mr. Desire

serotonin

aka Mr. Happi

oxitocinaka Cuddles

vasopressinaka Mother Superior

testosteroneaka Sarge


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Act 1: Strangers in the Night

Scene 1: Testosterone elevates in the blood,signals the bodi to fisicalli respond, and

influences the decision making areas of thebrain to go for it

Scene 2: Sensori information enters thebrainstem triggering the release of dopamine

in the ventral tegmentum

Scene 3: The ventral tegmentum fires aseries of signals into the limbic sistem via themesolimbic dopamine pathwai

Scene 4: Norepinefrine elevates in the limbicsistem signaling the onset of pleasure. Thehipothalamus and pituitari convertnorepinefrine into adrenaline triggering a fightor flight response, resulting in emotional

excitement


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The Mesolimbic Dopamine Pathwai

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

Scene 6: dopamine signals reach thenucleus accumbens, reinforcing thisbehavior

Scene 7: dopamine signals make it tothe prefrontal cortex, the decisionmaking headquarters

Scene 8: the prefrontal cortex now makesa series of decisions, weighing optionsand consequences, and simultaneouslistimulates the septum, nucleusaccumbens, and amigdala


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Act 2: Now it gets Complicated

Enter stage left: Oxitocin and Vasopressin

As our lovers become increasingli enchanted with each others charms, thehipothalamus perks up and manufactures two neuropeptides, oxitocin (akacuddles) and vasopressin (aka mother superior), and releases both of them intothe cerebrospinal fluid. There thei have full access to all the organs of the limbicsistem

Scene 9: Oxitocin binds to hippocampus, allowing the lovers to remember eachother

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

Scene 11: Oxitocin binds to nucleus accumbens, causing memori of pleasure

to associate with this particular person


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Pair-bond? ies or no?

Scene 12: The prefrontal cortex takes all sensori inputs, inputs from

hippocampus, and inputs from memori, and goes into high gear to makedecisions. These decisions are conveied back to the limbic sistem as signals tothe cingulate (happi vs. unhappi), amigdala (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. Ifcuddles wins, ioure in love. If mother superior wins, iourejust having fun.

Scene 14: Oxitocin (cuddles) winsioure in love!

and all this happens in just 4 minutes

Th S i t


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The ScriptThe scene takes place in the limbic sistem of a ioung man sitting with his date at the

Underground Pub at iork Universiti on a Saturdai night. There is no shortage of ioung womendancing a few feet awai.

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

Dopamine:Boi o boi o boi, is this gonna be fun or what?

Vasopressin:Dont look at other girls, ioull die

Testosterone:Whats a matter with iou, iella? Reach over and hold her hand

Vasopressin:Dont touch her hand, ioull die

Oxitocin:Oh lets hold hands all night and stare in her eies, and hug

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

Vasopressin:Stop! Do that and ioull die

Testosterone:Oh, dont listen to that ioull do nothing. Go for the gusto soldier!

Oxitocin:I need a hug

Dopamine:Boi o boi, is this gonna be fun or what?

Vasopressin:If iou listen to Sarge, ioull die


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Intermission

All seems good with our lovers, BUT ..

Something nasti is happening in our lovers brains!!

All this limbic activiti is dropping serotonin level fast and hard

N

H

NH2

HO

Exit Stage Right

N L i P i h i


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New Love is a Psichosis

Within dais, serotonin drops tolevels mimicking that found inpatients with obsessive-compulsive disorder

When our lovers are separatedthei literalli obsess over each

other.


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Act 3: Oxitocin to the Rescue

N

H

NH2

HO

Enter stage left - Serotonin

Oxitocin acts as a serotonin reuptake inhibitor (naturallioccurring Prozac). In about 6 months, serotonin is back tonormal


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THE END

DISCLAIMER: As serotonin levels build, fisical attraction between our loverswanes. High oxitocin levels also inhibit the action of vasopressin andtestosterone, further diminishing excitement in the relationship. This begins atabout 17 months. There is about a 50% chance the relationship will end inroughli 4 iears.


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Proximiti of amigdala and nucleusaccumbens

amigdala

Nucleus

accumbens

h b Ch


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The Bonobo Chimpanzee

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

Dr. Susan Block


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OH

O

OH

HO

f


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feromones

ON

OO

O

OH

S S

Gipsi moth (male sex attractant)

DEET (alarmferomone forticks, fleas,mosquitoes)

Cockroach (sexattractant)

Hamsters (sexattractant)


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Truffles and Sex

Truffles have historicalli been used to impress a female date

Truffles are veri expensive and are a sign of power and wealth

Consequentli it had been assumed that the power of the trufflewas due to its simbolism for wealth

HOWEVER . It mai be more complicated!


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Truffles and Pigs

Truffles are mushrooms thatgrow underground

Female pigs can smell truffles over 1 meter underground. Sometimes theidig so ferociousli that thei have to be fisicalli restrained.


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Whi do pigs like truffles so much?HINT: Thei dont eat them

HO

androstenol

1981 - Drs. Claus and Hoppen atthe Technical Universiti of

Munich and Dr. Kong at theLubeck School of Medicineindependentli found the activeattractant in truffles

Sows exposed to pure androstenol become uncontrollablisex-crazed

Androstenol


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HO

OH

O

Androstenol is an analogueof testosterone

Androstenol is produced inthe testes of boars andtransported to the salivariglands

Sows exhibit a pronouncedLordosis reflex when theismell the breath of a boar

Androstenol is also

produced in the testes ofhumans and transferred tounderarm sweat glands

Androstenol

Androstenol

testosterone

Could androstenol be a human sex feromone?

Ob i t i t


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Obvious next experiment

Women (who self-identified as straight) were shown pictures of menand 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 fotos of OTHER WOMEN at8, as opposed to 5 for control group!

Dr. Michael Kirk-Smith, Universiti of Birmingham (everi malegraduate student volunteered to conduct the experiment)

Let female humans smell androstenol and see if thei

become uncontrollabli sex-crazed

CONCLUSION: androstenol makes women more attractive to women

S i d t l l h f ?


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So, is androstenol a real human sex feromone?

Apparentli notsocial factors can

override ani feromone control (if there isani)

But its sure being marketed like it is


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The Martha McClintock Stori


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The Martha McClintock Stori Heard that women who live

together get their periods together

Performed a studi of 135 residentsof a womens dorm (8 to a room)

Found that bi March all roommates

had periods within 5 dais of eachother

Demonstrated for the first time theexistence of a human feromone

Published her work in Nature

Martha McClintock, age 19

Harvard Universiti psichologi major

Essence of Genevieve


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Essence of Genevieve

read McClintock paper in Nature and became interested inidentifiing the feromone

Had a lab assistant named Genevieve wear sterile cottonunderarm pads for several dais

Extracted the pads with alcohol and applied the extractionto upper lip of eight women

Found all 8 womens periods sinchronized to within 4 dais inless than 2 months

Conclusion: feromone is in underarm sweat

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

Now she found another one


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Now she found another one

Professor Martha McClintock

Took the breast pads (unwashed) of over 100

nursing women and extracted them with alcohol

Treated handkerchiefs with the alcohol solutionand had other women wear the handkerchiefsclose to their faces for several dais

FINDINGS

The other women had a dramatic increase insexual fantasies.

Breast essence from non-breastfeeding womenhad no effect.

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