kp-3!1!32-neurobiology of drug addiction

8/20/2019 Kp-3!1!32-Neurobiology of Drug Addiction

1/57

(NIDA.NEUROBIOLOGY O DRUG ADDICTION)

When a person first thinks about trying drugs, it is usually a voluntary decision. “Maybe I should see

what it’s like... just this once,” you ight think. !r a friend dares you. !r you just want to feel good

or forget your troubles. Most drugs of abuse " including nicotine, alcohol, arijuana, cocaine, and

heroin " activate a part of the brain called the reward system, and that akes you feel good. #ut just

for a little while. $rug abuse has serious conse%uences. &he ost serious conse%uence is that

prolonged drug use can change the brain in fundaental and long"lasting ways. 'ventually, it

becoes difficult to deerive pleasure fro other noral activities, such as sports, food, or se(. )fter repeated drug use, you reach a point when deciding to use drugs is no longer voluntary.

*cientists have proof now that drugs literally change your brain. It’s as if a “switch” goes off in the

brain. It is during this transforation process that adrug abuser becoes a drug addict .

)ddiction is a chronic relapsing disease characteri+ed by copulsive, often uncontrollable, drug

seeking and drug use in the face of negative conse%uences. $rug addicts need professional help

and treatent to help the cope with these changes and possibly change the brain back to noral.


2/57

NIDA.NEUROBIOLOGY OF DRUG ADDICTION. REWARD CONCEPT

&he brain is ade up of a cople( network of billions of nerve cells called neurons, as well as other

kinds of cells, all protected by the bones of the skull. &he typical brain weighs only about pounds,but it is the source of ost %ualities that ake you who you are. -eurons in the brain and

spinal cord are part of the nervous syste and act as a body’s “oand entral.”&he brain is

constantly active, even when we are asleep. )s a atter of fact, asleep or awake, the brain re%uires

/0 percentof the heart’s output of fresh blood and /0 percent of the blood’s o(ygen and glucose to

keep functioning properly. 1lucose is a type of sugar that is our brain’s priary fuel.

&he brain produces enough electrical energy to power a 20"watt light bulb for /2 hours.

&hat’s a lot of energy for a huan organ a little bigger than a softball.


3/57

The brain is your body

#rain controls all functions. &he brain controls our physical sensations and body oveents.

3ow we understand what we see, hear, sell, taste, and touch. !ur sense of balance and

coordination.Meory. 4eelings of pleasure and reward. &he ability to ake judgents. When we

catch a football, dance, jog, speak, sing, laugh, whistle, sile, cry " that’s our brain receiving,

processing, and sending out essages to different parts of our body.When we feel good for

whatever reason " laughing with a friend or seeinga good ovie or eating our favorite ice crea thebrain’s reward system is activated.&he reward syste is the part of the brain that akes you feel

good. &he reward syste is a collection of neurons that release dopaine, a neurotransitter.

When dopaine is released by these neurons, a person feels pleasure.*cientists have linked

dopaine to ost drugs of abuse " including cocaine, arijuana, heroin, alcohol, and nicotine.

&hese drugs all activate the reward syste and cause neurons to release large aounts of

dopaine. !ver tie, drugs daage this part of the brain. )s a result of this daage, things that

used to ake you feel good" like eating ice crea, skateboarding, or getting a hug " no longer feelas good.


4/57

The brain and spinal crd

The central nervous system is coposed

of both the brain and the spinal cord.

#rain is a functional unit5it is ade up of billions of nerve cells

6neurons7 that counicate with each other using electrical

and cheical signals.


5/57

How a neuron works

Illustration used with permission, courtesy of Lydia V. Kibiuk and the Society for Neuroscience


6/57

!OW A NEURON WOR" #E$PLANATION%

8 Neurons are unique because they can send information from the brain to the rest ofthe body. Your brain communicates with the rest of your body by sendin messaes

from one neuron to the ne!t and ultimately to the muscles and orans of the body.Neurons can also store information as memories.

8 "ypically, a neuron contains three important parts# a cell body that directs allacti%ities of the neuron& dendrites 'the part that looks like tree branches(, which areshort )bers that recei%e messaes from other neurons and relay those messaes tothe cell body& and the axon, a lon sinle )ber that transmits messaes from thecell body to dendrites of other neurons. *%ery moment, messaes are mo%in with

ama+in speed back and forth from neuron to neuron. s a matter of fact, scientistsoften compare the acti%ity of neurons to the way electricity works.

8 neuron communicates with other neurons at special placescalled synapses or synaptic clefts. "o send a messae, a neuron releases a chemicalmessener, or neurotransmitter , into the synaptic cleft. -rom there,the neurotransmitter crosses the synapse and attaches to key sites called receptorson the ne!t neuron in line. hen neurotransmitters attach to these receptors, they

cause chanes inside the recei%in neuron and the messae is deli%ered.8 Neurons communicate with each other throuh a network of interconnected cells

that scientists are still tryin to fully understand. Scientists do know that thiscomple! communication system within the brain can be disrupted by the chemicalsin drus. /id you know that more than 011 chemicals are in a mari2uana leaf3 ndo%er 0,111 chemicals besides nicotine are in tobacco4

8


7/57

Brain regions and neuronal a!"#a$s

Certain parts of the brain govern specific functions.

*ensory 6orange7, otor 6blue7 and visual corte( 6yellow7

erebellu 6pink7 for coordination. 3ippocapus 6green7 for eory.

Indicate that nerve cells or neurons connect one area to another via pathwaysto send and integrate inforation. &he distances that neurons e(tend can be short

or long. 9eward pathway 6orange7.&his pathway is activated when a person receives

positive reinforceent for certainbehaviors 6:reward:7. &his happens when a person

takes an addictive drug. &halaus 6agenta7. &his structure receives inforation

about pain coing fro the body 6agenta line within the spinal cord7,

and passes the inforation up to the corte(.


8/57

Control centers in the brain are affected by drug use

$rugs of abuse disable or disrupt iportant brain functions.

When soeone sokes arijuana, for e(aple, the cheical &3 6delta";"tetrahydrocannabinol7,

the ain psychoactive ingredient in arijuana, travels %uickly to the brain. We can see the areas of

the brain 6in dark blue7 where &3 concentrates.


9/57

%a!"#a$ &or sensa!ion o& ain and rea'!ion !o ain

&his is a long pathway, in which neurons ake connections in both the brain and

the spinal cord. !ne slas a door on one>s finger. 4irst, nerve endings in the finger

sense the injury to the finger 6sensory neurons7 and they send ipulses along a(ons

to the spinal cord 6agenta pathway7.. Incoing a(ons for a synapse with

neurons that project up to the brain. -eurons that travel up the spinal cord then

for synapses with neurons in the thalaus, which is a part of the idbrain

6agenta circle7. &halaus organi+es this inforation and sends it to the sensory

corte( 6blue7, which interprets the inforation as pain and directs the nearby otor corte(

6orange7 to send inforation back to the thalaus 6green pathway7. &halaus organi+es

this incoing inforation and sends signals down the spinal cord, which direct otor

neurons to the finger and other parts of the body to react to the pain6e.g., shaking the finger or screaing :ouch?:7.


10/57

Neuronal structure

These pathways are made up of neurons. &his iage contains real neurons fro

the thalaus. &hey have been filled with a fluorescent dye and viewed

through a icroscope. )natoy of a neuron@ ell body 6soa7, dendrites,

and a(on 6arked with te(t7.

)t the end of the a(on is the terinal, which akes a connection with another neuron.

A-ote@ the a(on has been drawn in for clarity, but actually, the a(ons of these neurons travel to the cerebral corte(.B


11/57

Impulse flow

The nr&al direc'in ( 'he )* ( in(r&a'in 'electrical andchemical(.

n electrical impulse 'the action potential( tra%els down the a!on toward theterminal. "he terminal makes a connection with the dendrite of neihborin neuron,where it passes on chemical information. "he area of connection is called thesynapse.lthouh the synapse between a terminal and a dendrite 'shown here(is quite typical, other types of synapses e!ist as well.


12/57

The synapse and synaptic neurotransmission

+,napse and 'he prcess ( che&ical ne-r'rans&issin. s an electrical impulsearri%es at the terminal, it triers %esicles containin a neurotransmitter, such as dopamito mo%e toward the terminal membrane. "he %esicles fuse with the terminal membrane ttheir contents 'in this case, dopamine(. 5nce inside the synaptic cleft'the space betweentwo neurons( the dopamine can bind to speci)c proteins called dopamine receptors 'in pi

on the membrane of a neihborin neuron..


13/57

Doaine neuro!ransission and odula!ion $ endogenous oia!es

Dopamine in synaptic function. It is synthesi+ed in the nerve terinal and packaged in vesicles.

In neurotransission, the vesicle fuses with the ebrane and releases dopaine.&he dopaine

olecules can then bind to a dopaine receptor 6in pink7. )fter the dopaine binds,it coes off the

receptor and is reoved fro the synaptic cleft by uptake pups 6also proteins7 that reside on theterinal 6arrows show the direction of oveent7.&his process is iportant because it ensures that

not too uch dopaine reains in the synapticcleft at any one tie. &here are neighboring

neurons that release another copound called a neuroodulator. -euroodulators help to

enhance or inhibit neurotransission that is controlled by neurotransitters such as dopaine. In

this case, the neuroodulator is an :endorphin: 6in red7. 'ndorphins bind to opiate receptors 6in

yellow7 which can reside on the post"synaptic cell6shown here7 or, in soe cases, on the terinals

of other neurons 6this is not shown so it ust be pointed out7. &he endorphins are destroyed byen+yes rather than reoved by uptake pups


14/57

A positron emission tomography (PET) scanner

-ow let’s take a look inside your ind... !ne of the tools that scientists use to see the effects of

drugs on the brain is called positron eission toography or a D'& say the word !pet"#scan.

*iilar to an ("ray, but uch ore sophisticated, a D'& scan is used to e(aine any differentorgans including the heart, liver, lungs, and bones, as well as the brain. ) D'& scan shows uch

ore than the physical structure of bone and tissue. ) D'& scan shows how well 6or how little7 an

organ is functioning.Esing a D'& scan, a doctor or a scientist can see what is actually happening in

a person’s brain and see the effects of drugs. &he D'& scan shows areas of the brain that are

active and also areas that are inactive or not functioning at all. &ypically, a D'& scan takes F to /

hours with the person lying copletely still so that the D'& iages will be clear.


15/57

This is literally the brain on drugs

Dhoto courtesy of -ora Golkow, Dh.$. Mapping cocaine binding sites in huan and baboon brain in vivo. 4owler

H*, Golkow -$, Wolf )D, $ewey *


16/57

Brain n dr-s/ e0plana'in8 When s&ene e's 1hih1 n ccaine/ *here des 'he ccaine

in 'he brain2 ith the help of a radioacti%e tracer, this 6*" scanshows us a person7s brain on cocaine and the area of the brain,hihlihted in yellow, where cocaine is 8bindin8 or attachin itself. "his6*" scan shows us minute by minute, in a time9lapsed sequence, 2usthow quickly cocaine beins a:ectin a particular area of the brain

8 e start in the upper left hand corner. You can see that ; minute aftercocaine is administered to this sub2ect nothin much happens. ll areasof the brain are functionin normally. the ne!tscan to the riht?, we see some areas startin to turn yellow. "hese

areas are part of a brain structure called the striatum >stry9a9tum? thatis the main taret in the brain bound and acti%ated by cocaine.

8 t the @9 to A9minute inter%al, we see that cocaine is a:ectin a larearea of the brain. fter that, the dru7s e:ects bein to wear o:. t theB9 to ;19minute point, the hih feelin is almost one. Cnless the abusertakes more cocaine, the e!perience is o%er in about D1 to =1 minutes.

8 Scientists are doin research to )nd out if the striatum produces the8hih feelin8 and controls our feelins of pleasure and moti%ation. 5neof the reasons scientists are curious about speci)c areas of the braina:ected by drus such as cocaine is to de%elop treatments for peoplewho become addicted to these drus. Scientists hope to )nd the moste:ecti%e way to chane an addicted brain back to normal functionin.


17/57

$ong%term effects of drug abuse

Dhoto courtesy of -ora Golkow, Dh.$. Golkow -$, 3it+eann 9, Wang 1"H, 4owler H*, Wolf )D, $ewey *


18/57

Ln 'er& e4ec's ( dr- ab-se/ e0plana'in

8 "his 6*" scan shows us that once addicted to a dru like cocaine,

the brain is a:ected for a lon, lon time. In other words, once

addicted, the brain is literally chaned. LetEs see how...

8 In this imae, the le%el of brain function is indicated in yellow. "he

top row shows a normal9functionin brain without drus. You cansee a lot of brain acti%ity. In other words, there is a lot of yellow

color.

8 "he middle row shows a cocaine addictEs brain after ;1 days

without any cocaine use at all. hat is happenin here3 Less yellow means less normal activity occurrin in the brain 9 e%en

after the cocaine abuser has abstained from the dru for ;1 days.

8 "he third row shows the same addictEs brain after ;11 days withoutany cocaine. e can see a little more yellow, so there is some

impro%ement 9 more brain acti%ity 9 at this point.


19/57

Drugs have long%term conse&uences

Dhoto courtesy of -I$) fro research conducted by Melega WD, 9aleigh MH, *tout $#,


20/57

Dr-s ha5e ln 'er& cnse6-ences

8 Fere is another e!ample of what science has shown us about thelon9term e:ects of drus. hat this 6*" scan shows us is how 2ust;1 days of dru use can produce %ery dramatic and lon9termchanes in the brain of a monkey. "he dru in these imaes isamphetamine, or what some people call Gspeed.H emember thepre%ious imae showed us what the brain of a chronic cocaineabuser looks like. "his imae shows us what usin a dru likeamphetamine can do in only ;1 days to the brain of a monkey.

8 "his imae also i%es us a better idea of what methamphetamine,a dru similar in structure, can do to the brain. Jethamphetamineuse is becomin increasinly popular in certain areas of thecountry.

8 "he top row shows us, in white and red, normal brain acti%ity. "hesecond row shows us that same brain 0 weeks after bein i%en

amphetamine for ;1 days. "here is a dramatic decrease in brainacti%ity. "his decreased brain acti%ity continues for up to ; yearafter amphetamine use. "hese continuous brain chanes oftentrier other chanes in social and emotional beha%ior, too,includin a possible increase in aressi%eness, feelins ofisolation, and depression.


21/57

The memory of drugs (cue)

Dhoto courtesy of )nna 9ose hildress, Dh.$.


22/57

The &e&r, ( dr-s #c-e%/ e0plana'in

8 "his imae demonstrates somethin really ama+in 9 how 2ust the mention ofitems associated with dru use may cause an addict to Gcra%eH or desire drus.

"his 6*" scan is part of a scienti)c study that compared reco%erin addicts, who

had stopped usin cocaine, with people who had no history of cocaine use. "hestudy hoped to determine what parts of the brain are acti%ated when drus arecra%ed.

8 -or this study, brain scans were performed while sub2ects watched two %ideos. "he )rst %ideo, a nondru presentation, showed nature imaes 9 mountains,ri%ers, animals, owers, trees. "he second %ideo showed cocaine and druparaphernalia, such as pipes, needles, matches, and other items familiar to

addicts.8 "his is how the memory of drus works# "he yellow area on the upper part of the

second imae is the amydala #a7&i7d-h7l-h%, a part of the brainEs limbicsystem, which is critical for memory and responsible for e%okin emotions. -oran addict, when a dru cra%in occurs, the amydala becomes acti%e and acra%in for cocaine is triered.

8 So if itEs the middle of the niht, rainin, snowin, it doesnEt matter. "his cra%in

demands the dru immediately . ational thouhts are dismissed by theuncontrollable desire for drus. t this point, a basic chane has occurred in thebrain. "he person is no loner in control. "his changed brain makes it almostimpossible for dru addicts to stay dru9free without professional help.


23/57

'ave you changed your mind

Dhoto courtesy of -I$). If =ou hange =our Mind. *tudent aga+ine. -I3 Dublication -o. ;"2J2, F;;.

3ere is our last iage. )s we look at side"by"side D'& scans of a person who has never usedcocaine copared with a cocaine addict, can you tell which brain is ore active and healthyL &ake

a guess. =es, the brain on the left with an abundance of red is the healthy, active brain.

&here will be no agic char to ake addiction go away. #ut educated and infored with the

scientific facts about what drugs can do to the brain, we are each in a better position to decide

whether or not to take drugs in the first place. 1iven the facts, have you changed your indL


24/57

A message to remember


25/57

+E+I "EDUA


26/57

Concept of reward. 3uans, as well as other organiss engage in behaviors

that are rewarding5 the pleasurable feelings provide positive reinforceent

so that the behavior is repeated.

&here are natural rewards as well as artificial rewards, such as drugs.


27/57

atural rewards such as food, water, se(, and nurturing allow the organis

to feel pleasure when eating, drinking, procreating, and being nurtured.

*uch pleasurable feelings reinforce the behavior so that it will be repeated.

'ach of these behaviors is re%uired for the survival of the species.

&here is a pathway in the brain that is responsible for rewarding behaviors.


28/57

T"e re#ard a!"#a$

Giew of the brain cut down the iddle. *eward pathway@ the ventral tegental area 6G&)7, thenucleus accubens, and the prefrontal corte(. &he G&) is connectedto both the nucleus

accubens and the prefrontal corte( via this pathway and it sends inforation to these structures

via its neurons. &he neurons of the G&) contain the neurotransitter dopaine, which is released

in the nucleus accubensand in the prefrontal corte(.&his pathway is activated by a rewarding

stiulus. A-ote@ the pathway shown here is not the only pathway activated by rewards, other

structures are involved too, but only this part of the pathway is shown for siplicity.B


29/57

s!iulus

Discovery of the *eward pathway. 9ats were trained to press a lever for a tiny electrical jolt

to certain parts of the brain. When an electrode is placed in the nucleus accubens,

the rat keeps pressing the lever to receive the sall electrical stiulus because it feels pleasurabl

&his rewarding feeling is also called positive reinforceent. !n area of the brain closeto the nucleus accubens. When the electrode is placed there, the rat will not press the lever

for the electrical stiulus because stiulating neurons in a nearby area that

does not connect with the nucleus accubens does not activate the reward pathway.

&he iportance of the neurotransitter dopaine has been deterined in these e(perients

because scientists can easure an increased release of dopaine in the reward pathway

after the rat receives the reward. )nd, if the dopaine release is prevented

6either with a drug or by destroying the pathway7, the rat won>t press the bar for the electrical jolt..


30/57

*eward+ drug self%administration


31/57

Concept of positive reinforcement or reward

9ats will press a lever to self"adinister an injection of cocaine or heroin that is inserted

into either the peripheral bloodstrea 6left iage7 or into specific brain regions 6right

iage7. &he rat keeps pressing to get ore cocaine or heroin because the drugs ake

the rat feel so good. &his is called positive reinforceent, or reward. -atural rewards

include food, water, and se( " each is re%uired to aintain survival of our species.

)nials and people will continue to e(hibit a behavior that is rewarding, and they will

cease that behavior when the reward is no longer present. '(plain that there is actually a

part of the brain that is activated by natural rewards and by artificial rewards such as

addictive drugs. &his part of the brain is called the reward syste. -euroscientists have

been able to pinpoint the e(act parts of the brain involved, with the help of the rats. Doint

to the cartoon on the right and e(plain that rats will also self"adinister addictive drugs

directly into their brains, but only into a specific area of the reward syste. If the injection

needle is oved less than a illieter away fro this crucial area, the rat won>t press

the lever for ore drug. *o based on inforation fro working with the rats, scientists

have drawn a ap of the brain, and located the structures and pathways that areactivated when an addictive drug is taken voluntarily. &ell the students that you will show

the this :ap.:


32/57

,n-ection of cocaine into the nucleus accumbens

$eonstrate how scientists located the structures iportant for the addictive nature ofdrugs. *how that a rat will self"adinister cocaine directly into the nucleus accubens

6or the G&)7 to activate the pathway. Doint to an area close to the nucleus accubens or

G&) and state that if the injection is placed in this other area, the rat will not press the

lever to receive the drug. Indicate that scientists know a lot ore than where the drug

acts to produce rewarding effects " they also know how the drugs work. *how e(aples

with cocaine, heroin, and arijuana.


33/57

rain regions and neuronal pathways

ertain parts of the brain govern specific functions. Doint to sensory, otor, association and visual

corte( to highlight specific functions. Doint to the hippocapus to highlight the region that is

critical for eory, for e(aple. Indicate that nerve cells or neurons travel fro one area to

another via pathways to send and integrate inforation. *how, the reward pathway. *tart at the

ventral tegental area 6G&)7 6in blue7, follow the neuronal path to the nucleus accubens

6purple7, and then on to the frontal corte(. &his pathway gets activated when a person receivespositive reinforceent for certain behaviors 6:reward:7, like taking an addictive drug.


34/57

Addiction is a state in which an organis engages in a compulsive behavior , even

when faced with negative conse%uences. &his behavior is reinforcing, or rewarding, as

you have just discussed. ) ajor feature of addiction is the loss of control in limitinginta/e of the addictive substance. &he reward pathway ay be even ore iportant

in the craving associated with addiction, copared to the reward itself. *cientists have

learned a great deal about the biocheical, cellular, and olecular bases of addiction5 it

is clear that addiction is a disease of the brain. *tate that you will provide two e(aples

of the interaction between drugs that are addictive, their cellular targets in the brain, and

the reward pathway.


35/57

+E+I "ETIGA


36/57

3eroin is an addictive drug, although not all users becoe addicted. 'nvironent and

the personality of the user are iportant in producing addiction. 3eroin produces

euphoria or pleasurable feelings and can be a positive reinforcer by interacting with the

reward pathway in the brain.

Localization of opiate binding sites within the brain and spinal cord


37/57

Localization of opiate binding sites within the brain and spinal cord

When a person injects heroin 6or orphine7, the drug travels %uickly to the brain through

the bloodstrea. )ctually, heroin can reach the brain just as %uickly if it is soked

6see description of iage /N7. )busers also snort heroin to avoid probles with needles.

In this case, the heroin doesn>t reach the brain as %uickly as if it were injected or soked, but itseffects can last longer. !nce in the brain, the heroin is converted to orphine by en+yes5

the orphine binds to opiate receptors in certain areas of the brain. )reas where opiates bind

6green dots7@ Dart of the cerebral corte(, the G&), nucleus accubens, thalaus, brainste,

and spinal cord are highlighted. Morphine binds to opiate receptors that are concentrated in areas

within the reward pathway 6including the G&), nucleus accubens, and corte(7.

Morphine also binds to areas involved in the pain pathway 6including the thalaus, brainste,

and spinal cord7. #inding of orphine to areas in the pain pathway leads to analgesia 6loss of pain7.


38/57

+or"ine inding #i!"in !"e re#ard a!"#a$

Morphine 6green dots7 binds to receptors on neurons in the G&) and

in the nucleus accubens, within the reward pathway.

Where opiat has its effects in the brain


39/57

Where opiat has its effects in the brain

Esing opiat as an e(aple, we can describe how drugs interfere with brain functioning. When a

person sokes, or injects opiat, it travels to the brain via the bloodstrea.)lthough it reaches all

areas of the brain, its euphoric effects are ediated in a few specific areas,especially those

associated with the reward pathway discussed in the previous iage. &he prefrontal corte( will be

heavely disturbed by opiat

p a es n ng o op a e recep ors n e nuc eus accum ens:i d d i l


40/57

increased dopamine release

&hree types of neurons participate in opiate action@ one that releases dopaine 6on the left7,a neighboring terinal 6on the right7 that contains a different neurotransitter 6probably 1)#) for

those who would like to know7, and the post"synaptic cell that contains dopaine receptors 6in

pink7. !piates bind to opiate receptors 6yellow7 on the neighboring terinal and this sends a signal

to the dopaine terinal to release ore dopaine. !ne theory is that opiate receptor activation

decreases 1)#) release, which norally inhibits dopaine release, so dopaine release is

increased.


41/57

Ra!s sel&,adinis!er "eroin

Hust as a rat will stiulate itself with a sall electrical jolt 6into the reward pathway7,

it will also press a bar to receive heroin. In this iage, the rat is self"adinistering heroin

through a sall needle placed directly into the nuclues accubens.

&he rat keeps pressing the bar to get ore heroin because the drug akes

the rat feel good. &he heroin is positively reinforcing and serves as a reward.

If the injection needle is placed in an area nearby the nucleus accubens,

the rat won>t self"adinister the heroin. *cientists have found that dopaine release

is increased within the reward pathway of rats self"adinistering heroin. *o, since ore

dopaine is present in the synaptic space, dopaine"dependent neurotransission

is augented, causing the activation of the reward pathway.


42/57

De&ini!ion o& !oleran'e

When drugs such as heroin are used repeatedly over tie, tolerance ay develop.

&olerance occurs when the person no longer responds to the drug in the way that person

initially responded. *tated another way, it takes a higher dose of the drug to achieve the sae level

of response achieved initially. 4or e(aple, in the case of heroin or orphine, tolerance develops

rapidly to the analgesic effects of the drug. A&he developent of tolerance is not addiction,

although any drugs that produce tolerance also have addictive potential.B &olerance to drugs can

be produced by several different echaniss,but in the case of orphine or heroin, tolerance

develops at the level of the cellular targets. 4or e(aple, when orphine binds to opiate receptors,

it triggers the inhibition of an en+ye6adenylate cyclase7 that orchestrates several cheicals

in the cell to aintain the firing of ipulses. )fter repeated activation of the opiate receptor

by orphine, the en+ye adapts so that the orphine can no longer cause changes in cell firing.

&hus, the effect of a given dose of orphine or heroin is diinished.

rain regions mediating the de!elopment of morphine tolerance


43/57

g g p p

&he developent of tolerance to the analgesic effects of orphine involves different areas of the

brain separate fro those in the reward pathway. Doint to the two areas involved here, the

thalaus, and the spinal cord 6green dots7. #oth of these areas are iportant in sending pain

essages and are responsible for the analgesic effects of orphine. &he parts of the reward

pathway involved in heroin or orphine addiction are shown for coparison.

"efinition of dependence


44/57

p

With repeated use of heroin, dependence also occurs. $ependence develops when the

neurons adapt to the repeated drug e(posure and only function norally in the presence

of the drug. When the drug is withdrawn, several physiologic reactions occur. &hese can

be ild 6e.g., for caffeine7 or even life threatening 6e.g., for alcohol7. &his is known as the

withdrawal syndroe. In the case of heroin, withdrawal can be very serious and the

abuser will use the drug again to avoid the withdrawal syndroe.

ra n reg ons me a ng e e!e opmenof morphine dependence


45/57

of morphine dependence

&he developent of dependence to orphine also involves specific areas of the brain,

separate fro the reward pathway. In this case, point to the thalaus and the brainste 6green dots7

&he parts of the reward pathway involved in heroin or orphine addictionare shown for coparison.

Many of the withdrawal syptos fro heroin or orphine are generated when the opiate receptors

in the thalaus and brainste are deprived of orphine.

Addi'!ion *s deenden'e


46/57

$ifferent parts of the brain are responsible for the addiction and dependence to heroin and opiates.

)reas in the brain underlying the addiction to orphine 6reward pathway7 and those underlying

the dependence to orphine 6thalaus and brainste7. &hus, it is possible to be dependent

on orphine, without being addicted to orphine. 6)lthough, if one is addicted, they are ost likelydependent as well.7 &his is especially true for people being treated chronically with orphine,

for e(aple, pain associated with terinal cancer. &hey ay be dependent " if the drug is stopped,

they suffer a withdrawal syndroe. #ut, they are not copulsive users of the orphine, and

they are not addicted. 4inally, people treated with orphine in the hospital for pain control after

surgery are unlikely to becoe addicted5 although they ay feel soe of the euphoria,

the analgesic and sedating effects predoinate. &here is no copulsive use and the prescribed useis short"lived.


47/57

+E+I "EE8PAT

T"e a'!ion o& 'o'aine


48/57

ocaine is also an addictive drug, and like heroin, not all users becoe

addicted. 3owever, with the advent of crack cocaine 6the freebase7,the rate of addiction to cocaine has increased considerably.

#norting !s smoking cocaine: different addicti!e liabilities


49/57

3istorically cocaine abuse involved snorting the powdered for 6the hydrochloride salt7.

When cocaine is processed to for the freebase, it can be soked. 3eating the hydrochloride salt

for of cocaine will destroy it5 the freebase can be volatili+ed at high teperature without any

destruction of the copound. *oking gets the drug to the brain ore %uickly than does

snorting. *norting re%uires that the cocaine travels fro the blood vessels in the nose to the heart6purple arrow7, where it gets puped to the lungs 6purple arrow7 to be o(ygenated.

&he o(ygenated blood 6red arrows7 carrying the cocaine then travels back to the heart where

it is puped out to the organs of the body, including the brain. 3owever, soking bypasses uch

of this, the cocaine goes fro the lungs directly to the heart and up to the brain. &he faster a drug

with addictive liability reaches the brain, the ore likely it will be abused.&hus, the tie between

taking the drug and the positive reinforcing or rewarding effects that are produced can deterine

the likelihood of abuse.

Lo'ali-a!ion o& 'o'aine inding si!es


50/57

When a person sokes or snorts cocaine, it reaches all areas of the brain,but it binds to sites in soe very specific areas. &hese are highlighted with

the yellow dots@ the G&), the nucleus accubens, and the caudate nucleus

6the largest structure7. ocaine binds especially in the reward areas .

&he binding of cocaine in other areas such as the caudate nucleus can

e(plain other effects such as increased stereotypic 6or repetitive7 behaviors

6pacing, nail"biting, scratching, etc..7

Where cocaine has its effects in the brain


51/57

Esing cocaine as an e(aple, we can describe how drugs interfere with brain

functioning. When a person snorts, sokes, or injects cocaine, it travels to the brain via

the bloodstrea.)lthough it reaches all areas of the brain, its euphoric effects are

ediated in a few specific areas,especially those associated with the reward pathway

discussed in the previous iage.

"opamine binding to receptors$and uptake pumps in thenucleus accumbens: the action of cocaine


52/57

and uptake pumps in thenucleus accumbens: the action of cocaine

ocaine binds to sites in areas of the brain that are rich in dopaine synapses such

as the G&) and the nucleus accubens. 9eview dopaine transission in the close"up of asynapse in the nucleus accubens. Doint to dopaine 6inside the terinal7 that is released into the

synaptic space. &he dopaine binds to dopaine receptors and then is taken up by uptake pups

back into the terinal. -ow show what happens when cocaine is present 6yellow7. ocaine binds to

the uptake pups and prevents the fro transporting dopaine back into the neuron terinal. *o

ore dopaine builds up in the synaptic space and it is free to activate ore dopaine receptors.

&his is the sae effect that you showed in an earlier iage with orphine, where orphine

increased dopaine release fro the terinal to produce ore dopaine in the synaptic space.

%ocaine dependence and acti!ation of the reward pathway


53/57

ocaine binds within the reward pathway 6the G&) and the nucleus accubens7. )s a result of

cocaine>s actions in the nucleus accubens 6the dots of cocaine in the G&) and nucleus

accubens7, there are increased ipulses leaving the nucleus accubensto activate the reward

syste. &his pathway can be activated even in the absence of cocaine 6i.e., during craving7.

Indicate that with repeated use of cocaine, the body relies on this drug to aintain rewarding

feelings. &he person is no longer able to feel the positive reinforceent or pleasurable feelings of

natural rewards 6i.e. food, water, se(7""the person is only able to feel pleasure fro the cocaine.

&hus the user becoes dependent and when the cocaine is no longer present, anhedonia

6inability to feel pleasure7 and depression eerge as part of a withdrawal syndroe. &o avoid this,

the user goes back to the cocaine. Enlike the e(aple for orphine, cocaine addiction 6i.e.,craving7 and dependence 6i.e., anhedonia7 both involve structures in the reward pathway.

&ats self'administer cocaine


54/57

*cientists have easured increased dopaine levels in the synapses of the rewardpathway in rats self"adinistering cocaine. Hust as they did for heroin, rats will press a

bar to receive injections of cocaine directly into areas of the reward pathway such as the

nucleus accubens and the G&). )gain, if the injection needle is placed near these

regions 6but not in the7, the rat will not press the bar to receive the cocaine. &he ability

of rats to self"adinister cocaine is an e(cellent predictor of the addictive potential of this

drug.

(easuring brain acti!ity in response to drug use


55/57

Dosition 'ission &oography 6D'&7 easures eissions fro radioactively"labeled cheicals

that have been injected into the bloodstrea, and uses the data to produce iages of thedistribution of the cheicals in the body.In drug abuse research, D'& is being used for a variety of

reasons including@ to identify the brain sites where drugs and naturally occurring neurotransitters

act5 to show how %uickly drugs reach and activate receptors5 to deterine how long drugs occupy

these receptors5 and to find out how long they take to leave the brain.D'& is also being used to

show brain changes following chronic drug abuse, during withdrawal fro drug use, and during the

e(perience of drug craving. In addition, D'& can be used to assess the effects of pharacological

and behavioral therapies for drug addiction on the brain.

Psi'rn e&issin '&raph, #PET% scan ( a persn n


56/57

p , # % pccaine

ocaine has other actions in the brain in addition to acti%atin reward.ocaine actually a:ects brain function in people. "he 6*" scan allows one tosee how the brain uses lucose& lucose pro%ides enery to each neuron so it

can perform work. "he scans show where the cocaine interferes with thebrain7s use of lucose 9 or its metabolic acti%ity. "he left scan is taken from anormal, awake person. "he red color shows the hihest le%el of lucoseutili+ation 'yellow represents less utili+ation and blue shows the least(. "heriht scan is taken from a cocaine abuser on cocaine. It shows that the braincannot use lucose nearly as e:ecti%ely 9 show the loss of red compared to

the left scan. "here are many areas of the brain that ha%e reduced metabolic7

#ummary: addicti!e drugs acti!ate the reward system !ia increasing dopamine neurotransmission


57/57

In this last iage, the reward pathway is shown along with several drugs that have addictive

potential. Hust as heroin or orphine and cocaine activate the reward pathway in the G&) and

nucleus accubens, other drugs such as nicotine and alcohol activate this pathway as well,although soeties indirectly 6point to the globus pallidus, an area activated by alcohol that

connects to the reward pathway7. )lthough each drug has a different echanis of action, each

drug increases the activity of the reward pathway by increasing dopaine transission. #ecause of

the way our brains are designed, and because these drugs activate this particular brain pathway for

reward, they have the ability to be abused. &hus, addiction is truly a disease of the brain.

)s scientists learn ore about this disease, they ay help to find an effective treatent strategy for

kp-3!1!32-neurobiology of drug addiction

Documents