The Role of Dopamin

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ww w.f rontiersin.o rg May 2014 | Volume 5 | Article 47 |Frontiers in Psychiatry | Schizophrenia May 2014 | Volume 5 | Article 47 |

PSYCHA!"Y

"#V#$ A"!C%#pu&li'he() 1* May 2014

(oi) 10+,,-*./p'yt+2014+00047

!he role o/ (opamine in 'chizophrenia /rom aneuro&iolo0ical an( e1olutionary per'pecti1e) ol(

/a'hione(2&ut 'till in o0ue

RalfB ris ch1 *, A r thurSaniotis 2,3 , RainerWolf 4, Hendrik Bielau 5,Hans-GertBernstein5,ohannSteiner5,BernhardBo!erts5,"atharinaBraun #,$%i!nie& anko&ski 1, ali'a "u(aratilake), acie+ Henne%er!)

and ,o(as- Gos 1

1 Department of Forensic Medicine,Medical University of Gdansk, Gdansk, Poland2 School of Medical Sciences, The University of delaide, delaide, S, !stralia" #entre for $vol!tionary Medicine, University of %!rich, %!rich, S&it'erland( Department of Psychiatry and Psychotherapy,)!hr University *och!m, *och!m, Germany+ Department of Psychiatry, tto-von-G!ericke-University of Ma.de/!r., Ma.de/!r., Germany0 Department of %oolo.y, 1nstit!te of *iolo.y, tto-von-G!ericke-University of Ma.de/!r., Ma.de/!r., Germany *iolo.icalnthropolo.y and #omparative natomy )esearch Unit, School of *iomedical Sciences, The University of delaide, delaide, S, !stralia

.dited %'/

Thomas 34 3eickert, University of

5e& So!th 3ales,!stralia

Re0ie&ed %'/Michael Min'en/er., University of

#alifornia Davis School of

Medicine, US

ssen 6eniaminov 7a/lensky,

The University of 3estern

!stralia,!stralia

*orres2ondence/

)alf *risch, Department of Forensic

Medicine,Medical University of

Gdansk, !l4De/o&a 2", Gdansk

P8-9:-2:(, Poland

e-mail; ralf/ris ch< hotmail4com

3opamine i' an inhi&itory neurotran'mitter inole( in the patholoy o/ 'chizophrenia+ !he

rei'e( (opamine hypothe'i' 'tate' that (opamine a&normalitie' in the me'olim&ic an(

pre/rontal &rain reion' ei't in 'chizophrenia+ Hoeer recent re'earch ha' in(icate(

that lutamate 6AA acetylcholine an( 'erotonin alteration' are al'o inole( in the

pathol8 oy o/ 'chizophrenia+ !hi' reie proi(e' an in8(epth analy'i' o/ (opamine in

animal mo(el' o/ 'chizophrenia an( al'o /ocu'e' on (opamine an( conition+

9urthermore thi' reie proi(e' not only an oerie o/ (opamine receptor' an( the

antip'ychotic e//ect' o/ treatment' taretin them &ut al'o an outline o/ (opamine an( it'

interaction ith other neurochemical mo(el' o/ 'chizophrenia+ !he role' o/ (opamine in

the eolution o/ the human &rain an( human mental a&ilitie' hich are a//ecte( in

'chizophreniapatient' are al'o (i'cu''e(+

Keywords: dopamine, schizophrenia, cognition, glutamate, dopamine receptors, cannabis, animal models of

schizophrenia, evolution of the human brain

B!"F #!$%&' &F (&P)*!+" #'P&%#"$!$ !+

$,#!-&P#"+!)3opamine a(renaline an( nora(renaline are neurotran'mitter'

that &elon to the catecholamine /amily+ 3opamine i'pro(uce(

in the 'u&'tantia nira an( entral temental reion' o/ the &rain

an( (opamine alteration' are relate( to 'chizophrenia :1 2;+

3opamin8 eric pro


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ri'ch et al+ !he role o/ (opamine in 'chizophreniari'ch et al+ !he role o/ (opamine in 'chizophrenia

/or emotional proce''in :24;+ P#!8'tu(ie' :po'itron emi''ion

tomoraphy; hae i(enti/ie( (i//erence' in (opamine content' in

the pre/rontal corte cinulate corte an( hippocampu'

&eteen 'chizophrenia patient' an( neurop'ychiatric healthy

control 'u&8


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Val15- allele 'ho &etter conitie a&ilitie' inclu(in

eecutie proce''in an( conitie /lei&ility than carrier' o/ the

Met allele :-7;+

(&P)*!+" ","P%&$ )+( )+%!P$',#&%!, "FF",%$ !+

$,#!-&P#"+!)

3opamine receptor' are 68protein8couple( receptor' an( can&e

(ii(e( into 3 :1; 3 :2; 3 :,; an( 3 :4;8receptor' :--;+ 3

:1; receptor' in the pre/rontal corte are (ecrea'e( in 'chizophre8

nia patient' an( are una//ecte( &y chronic treatment o/ typicalneuroleptic' Greie &y 9rie(mann et al+ :-*;+ n contra't 3

:1;8receptor' are increa'e( in the parieto8temporal corte in

'chiz8 ophrenia patient' :*0;+ ncrea'e( 32 m"A ha' &een

/oun( in the /rontal corte in 'chizophrenia patient' hen

compare( ith neurop'ychiatric healthy control 'u&


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:145;+ !he actiity o/ (opamine i' reulate( &y 6AA an( luta8

mate+ 9or eample cortico'triatal lutamateric pathay'

interact ith (opamine terminal' :14@ 147; an( 'peci/ic

lutamate recep8 tor' in the 'triatum 'uch a' m6lu2 are

'en'itie to (opamine :112;+ Hih lutamate leel' hae &een

/oun( in the (or'al cau(ate nucleu' o/ 'chizophrenia patient'

:14-;+ A(eno'ine interact' ith lutamate M3A8receptor'

an( (opamine Greie &y urn'tocE et al+ :14*;+ t can &e

'ummarize( that M3A8receptor' an( 3 :1;8receptor' in

cortical &rain area' 'uch a' the pre/rontal corte an( an ece'' o/

3 :2;8receptor' in 'u&cortical &rain area' 'uch a' the 'triatum

are interconnecte( ith each other throuh apo'i8 tie /ee(&acE

mechani'm :150;+ Hoeer throuh it' pre'ynaptic action

(opamine re(uce' the relea'e o/ lutamate in the pyrami8 (al

neuron' o/ layer V in the pre/rontal corte :151;+ 3opamine

(y'reulation in the &a'al anlia o/ 'chizophrenia patient' i' an

important intrin'ic /eature in the patholoy o/ 'chizophrenia an(

not a me(ication 'i(e e//ect Greie&y Perez8Co'ta' et al+ :,;+

!he /in(in &y ri'ch et al+ :152; that a'trocyte (en'ity i'

increa'e( in the /rontal corte in 'chizophrenia 'ue't' a (i'8

tur&ance in the (opamine=lutamate /unction+ 9urthermore

SoEolo// et al+ :15,; (emon'trate( that 3 :,;8receptor' either

act (irectly on M3A8receptor' at lutamate 'ynap'e' on theterminal' o/ pyrami(al cell' in the nucleu' accum&en' or act

in(irectly throuh (opamine at the pre'ynaptic


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an( hypolutamateric actiitie' ith &oth po'itie an( nea8

tie 'ymptom' :21@;+ n particular canna&i' increa'e' (opamine

tran'mi''ion in the nucleu' accum&en' hich miht cau'e or

araatep'ycho'e' :217;+ A hih8lo actiity polymorphi'm in

CBM! interact' ith a(ole'cent canna&i' a&u'e increa'in the

ri'E /or 'chizophrenia :21-;+ 9urther ene' 'uch a' (i'rupte(8in8

'chizophrenia81 :3SC1; play a role in 'tre'' pathay' an( the

meta&oli'm o/ (opamine in 'chizophrenia Greie &y Hain' an(

Arn'ten :21*; %ipina et al+ :220;+

(&P)*!+" )+( #0*)+ "2&.0%!&+

!he role o/ (opamine in human eolution ha' hitherto receie(

lit8 tle theoretical attention+ t i' 'till unclear to hat etent

(opamin8 eric epan'ion in hominin eolution a' (ue to

enetic a(apta8 tion' or epienetic /actor'+ 3opamine ha'

epan(e( throuhout primate an( hominin eolution an( that

(opamine i' e'pecially concentrate( in the pre/rontal corte

hich i' inole( in hiher or(er /unctionin+ !he (opamineric

hypothe'i' conten(' that cli8 matic chane' occurrin in 'u&8

Saharan A/rica (urin the Pliocene an( Plei'tocene perio('

hich re'ulte( in increa'e' o/ the Saan8 nah &elt epan(e(

hominin locomotory rane+ t i' al'o 'peculate( that 'ome humanroup' enture( to the more ha&ita&le A/rican 'outhern coa't

lea(in to (ietary chane' :i+e+ increa'in amount' o/

/i'h.'hell/i'h; that ai(e( (opamineric epan'ion :221=22,;+

3opamine increa'e may hae al'o &een linEe( ith a

concomitant eleation in thyroi( hormone pro(uction+ Hiher

!4 /oun( in =omo may hae repre'ente( an early

en(ocrinoloical (i//erence&eteen human' an( other primate'

:224;+ n human' !4 concen8 tration i' a''ociate( ith tyro'ine

coner'ion to (opa :aprecur'or to (opamine; (e/iciencie' o/ !4

concentration' are linEe( ith ariou' neuroloical impairment'

:224;+

"ecent re'earch 'ue't' that /rom =omo erect!s onar(

human' &ecame per'i'tence hunter' reFuirin ariou' morpho8loical an( thermo8reulatory mo(i/ication' :i+e+ a'cular reac8

tiity to temperature lare &o(y 'ur/ace area plantar arch;

hichproi(e' approimately 20J enery return (urin runnin

ela'tic ten(on' 'hort toe' more pronounce( .l!te!s ma>im!s

mu'cle lon le' CS coor(ination o/ meta&olic an( car(io8

a'cular re'pon'e' to 'u'taine( runnin :225;+ 9rom =omo

erect!s onar( there i' an ei(ent increa'e in 'tri(e 'ize hich

al'o optimize( eronomic reFuirement' o/ &ipe(ali'm hile

(imini'hin enery reFuirement'+ 6reater ma'' o/ 'lo titch

mu'cle' oul( hae al'o a''i'te( lon (i'tance locomotion+ %on

(i'tance locomotion in con


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25+ Patel H Vya' S Puri K ip Ther :2012; 676)2--=

*5+ (oi)10+1124.


7/16

45+ Simp'on #H $altz LA2 Kellen(onE C al'am P3+ Schizophrenia in tran'la8

tion) (i''ectin motiation in 'chizophrenia an( ro(ent'+ Schi'ophr *!ll :2012;

63)1111=7+ (oi)10+10*,.'ch&ul.'&'114

4@+ ay


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@5+ 6ro'' 6 $icEe K 3re'cher KI+ 3opamine 3:,; receptor antaoni'm8'till

a therapeutic option /or the treatment o/ 'chizophrenia+ 5a!nyn

Schmiede/er.s rch Pharmacol :2012; 639:2;)155=@@+ (oi)10+1007.'002108

01280-0@8,

@@+ Micheli 9 Hei(&re(er C+ 3opamine 3, receptor antaoni't') a pa tent

reie :200782011;+ $>pert pin Ther Pat :201,; 46:,;),@,=-1+

(oi)10+1517.

1,54,77@+201,+7575*,

@7+ A&i83arham A Malai B %om&ar(o 6il " Martinez 3 Huan Y2 et

al+

Pre/rontal (opamine 31 receptor' an( orEin memory in 'chizophrenia+ 75e!rosci :2002; 144),70-=1*+

@-+ Stra//ella AP Pau' ! 9raraccio M 3aher A+ Striatal (opamine relea'e

in(uce(&y repetitie tran'cranial manetic 'ti m ulation o/ thehuman motor

corte+*rain :200,; 149)2@0*=15+ (oi)10+10*,.&rain.a2@-

@*+ Sumiyo'hi ! Hiuchi Y2 Iehara !+ eural &a'i' /or the a&ility o/

atypical antip'ychotic (ru' to improe conition in 'chizophrenia+ Front

*ehav5e!- rosci :201,; 5)140+ (oi)10+,,-*./n&eh+201,+00140

70+ Artia' 9+ !he pre/rontal corte ) a taret /or antip' y c hotic ( ru '+cta

Psychiatr

Scand :2010; 141)11=21+ (oi)10+1111.


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rei'e( mechani'm an( (e'cription o/ the the r mola&ile a r iant o/ the

enzyme+

*iochemistry :1**5; 67)4202=10+ (oi)10+1021.&i0001,a00-

-@+ Mattay VS2 6ol(&er !# 9era 9 Hariri A" !e''itore A #an M9 et al+

Catechol8 B8methyl8tran'/era'e al15-8met enotype an( in(ii(ual

ariation in the&rain re'pon'e to amphetamine+Proc 5atl cad Sci U S

:200,; 188)@1-@=*1+ (oi)10+107,.pna'+0*,1,0*100

-7+ Soli'8Brtiz S Perez8%uFue # Mora(o8Cre'po % 6utierrez8Munoz M+

#ec8 utie /unction' an( 'electie attention are /aore( in mi((le8ae(

healthy omen carrier' o/ the Val.Val enotype o/ the catechol8B8

methyltran'/e ra'e ene) a &ehaioral enetic 'tu(y+ *ehav *rain F!nct

:2010; 9)@7+ (oi)10+11-@.

17448 *0-18 @8

@7--+ !rit'ch Sa&atini 7%+ 3opamineric mo(ulation o/ 'ynaptic t ran'mi''ion

in corte an( 'triatum+ 5e!ron :2012; 59),,=50+

(oi)10+101@.


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10@+ Samaha A8 "ecEle'' 6# Seeman P 3ian M o&rea L Kapur S+ %e''

i' more) antip'ychotic (ru e//ect' are reater ith tran'ient r ather than

contin8 uou' (eliery+ *iol Psychiatry :200-; 97)145=52+

(oi)10+101@.


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'chizophrenia+5e!ropsychopharmacolo.y :2004; 4;)127+ (oi)10+10,-.'


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14-+ (e la 9uente8San(oal C %eWn8Brtiz P 9aila " Stephano S Mamo

3 "amXrez8erm(ez L et al+ Hiher leel' o/ lutamate in the

a''ociatie8 'triatum o/ 'u&


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antip'ychotic aent' on a'trolial /unction'+ $!r rch Psychiatry #lin

5e!rosci

:2010; 498)475=-1+ (oi)10+1007.'0040@8 00*800*580

1@-+ Ser'hen H alla A A'promonte LM ie S Cooper ! Laitt 3C+ Charac8

terization o/ interaction' &eteen phencycli(ine an( amphetamine in ro(ent

pre/rontal corte an( 'triatum) implication' in M3A.lycine8'ite8me(iate(

(opamineric (y'reulation an( (o pamine tr an'po r ter /unction+

5e!rochem nt :200-; 4)11*=2*+ (oi)10+101@.


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225+ Matt'on MP+ #olutionary a'pect' o/ human e e rci'e= &o r n to r un

purpo'e8 /ully+.ein. )es)ev :2012; 11),47=52+

(oi)10+101@.

The Role of Dopamin

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