Russia_Guidelines for Abuse Liability Evaluation

Russia_Guidelines for Abuse Liability Evaluation

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paCTBopa a.z:L1lI1KTI1BHOrO COenl1HeHIDI I1CCJIenOBaTeJIhCKa5l peaKUI15l He yraIIIa­
eTC5l, a, HanpOTI1B, O)l(I1BJUIeTC5l, TaK KaK JolCCJIenyeMhIM npenapaT 06JIanaeT
"aTTpaKTI1BHhIMI1" MOTI1BaUI10HHhIMI1 CBoMCTBaMI1. B3)I(HhIM 3JIeMeHTOM Me­
Tona 5lBJUIeTC5l I1CnOJIh30BaHI1e naphl MhlIIIeM, OtJ;Ha 113 KOTOpbIX 5lBJI5leTC5l "aK­
TI1BHOM" (AM), 11 ee BhlrJIMbIBaHIDl B OTBepCTl1e npI1BOLI5lT K BHyTpI1BeHHOM
caM0l1HcPY31111 I1CCJIetJ;yeMoro paCTBopa, a TaK)l(e K I1HcPY31111 TOM )I(e n03hl B
BeHy BTOPOM, KOHTpOJIhHOM MblIIII1 (KM). IToCJIenHAA, TaKI1M 06pa30M, nOJIy­
'iaeT I1HcPY31111 I1cCJIenyeMoro COenl1HeHIDI B TOM )I(e pe)l(I1Me, 'iTO 11 AM, HO
3TO BBetJ;eHl1e 5lBJI5leTC5l npI1HYtJ;I1TenbHbIM, a He "caMOBBeneHl1eM", TaK KaK
OHO He 3aBI1CI1T OT co6CTBeHHOM 0pl1eHTl1pOBO'iHO-I1CCJIetJ;OBaTeJIbCKOM peaK­
UI1I1 KOHTponbHoro )I(I1BOTHoro. ¥ICnOJIh30BaHl1e KM n03BOJUIeT OueHI1BaTh
BJII15lHl1e I1ccnenyeMoro npenapaTa Ha 06111ee nOBeneHl1e, B 'iaCTHOCTI1 Ha
ypoBeHh I1CCJIenOBaTeJIhCKOH: peaKUI1I1.
- 322­
!
I
CTI1 B Ka)I(t(OM rpynne 6bW no B03MO)I(HOCTI1 6n113KI1M.
KaK nOKa3hIBaeTOnhIT, I1HI1Ul1aUIDI PBC KaK "6onhIIIl1x" (MOPcP I1H , KOK3I1H,
aMcP e
TaMI1H, 3cP etJ;pOH), TaK 11 "MaJIhIX" (HI1KOTl1H, K0cPeI1H, 3TaHon) antJ:I1KTI1B­
HhIX cpetJ;cTB npOI1CxotJ;I1T B Te'ieHl1e 10-20 MI1H. IT03TOMY 06IUa5l npOLIOJI)l(J1­
TeJIhHOCTh ceccl1l1 C BhIpa6oTKoM PBC COCTaBJUIeT 30 MI1H. ITpeLIBapl1TeJIhHO
oT06paHHhle naphI MhIllieli nOMelllalOT B 3KCnepl1MeHTaJIhHhIe 60KChl 11 nocne
3-4 MI1H ananTaUl111 B JIaTepaJIhHhIe XBOCTOBhIe BeHhI 06el1x MblliIeH: BBOLI5lT
I1rJIhI, notJ;coetJ;I1HeHHhIe K I1HbeKTOpy 'Iepe3 nOJIl13TI1JIeHOBhle KaTeTephI. Bo
BpeM5l 30-MI1HYTHOM ceCC1111 BhIpa60TKI1 PBC "aKTI1BHa5l MhIlllh" (AM) nOJIY'la­ eT BHyTpl1BeHHhIe I1HbeKUl111 I1ccnemeMoro pacTBopa nocne Ka)l(t(OrO BhIrJIMbl­ BaHIDI. KOHTpOJIhHa5l "naCCI1BHa5l MhIlllh" (KM) nOJIyqaeT I1HbeKUl111 B pl1TMe
BbIrJIMhIBaHI1M AM, HO BHe CB5l311 C co6CTBeHHhIMI1 BhIrJI5lt(hIBaHIDIMI1. TaKl1M
06pa30M, 06a )I(I1BOTHbIX nOJIyqalOT Onl1HaKOBOe 'II1CJIO I1HbeKUI1M C OtJ;I1HaKO­
BhIM pacnpetJ;eJIeHl1eM I1HbeKUI1H: BO BpeMeHI1 11, COOTBeTCTBeHHO, OtJ;I1HaKOByIO
tJ;03Y npenapaTa, 'ITO n03BOJUIeT npl1 oueHKe 3cPcPeKTa 11 cpaBHeHl111 tJ;aHHhIX Y
AM 11 KM "ypaBH5lTh" BJIIDlHl1e npenapaTOB Ha tJ;Bl1raTenhHyIO 11 I1CCnetJ;OBa11­
- 323­
1\
I:
,;
I'
IIpoaOflJiCexue
TeJIbCKYIO aKTI1BHOCTb. TIo OKOHqaHl111 30 MI1H I1rJIbI 113BJIeKalOT 11 )KI1BOTHbIX
B03BpalllalOT B o6111YIO KJIeTKY.
3aKJIIO'leHl1e 0 rrOJIO)KMTeJIbHO-rrOl[KpeIIJUIlOllleM 3<p<peKTe I1CCJIel[yeMoro co­
el[I1HeHlliI OCHOBbIBalOT Ha paCXO)Kl[eHI1I1 KOJIl1'1eCTBa Bblrllil.l[bIBaHllH (KB) AM
M KM. ECJIll 3a rrepl1ol[ ceCCCllll KB AM rrpeBbIlllaeT KB TIM, TO l[eJIalOT 3a­
KJIIOQeHlle 0 MOTllBaUMOHHO-rr03llTMBHOM (rrOJIO)KI1TeJIbHO-rrOl[KpeII.JI>IlOllleM)
3<p<peKTe COe,UI1HeHI151. ECJII1 K.B AM B rrepl10l[ ceccl1l1 MeHbllle rro CpaBHeHlllO
C KB TIM, TO 3<p<peKT COel[I1HeHlliI paCueHMBalOT KaK "aBepCI1BHbIH" ("HaKa­
3YlOlllMH").
HCT orpaHI1'leHllt! B nyT51X BBClleHl1il
Hccne.nyeMhlx BCWCCTB
OnHOBpeMeHHO ouc­
HI1BalOTcil KaK "aT­
TpaKTI1BHblC", TaK H
aBepcllBHhlC CBoll!CT­
Ba I1ccJlc.nycMoro Be­
lUeCTBa
3<I><I>EKTIIBHOCTh lICIIOnh30BAHIDI METO)l,A
KPI1Ba5l 3aBI1CI1MOCTM "KOHueHTpaUI15l-3<p<peKT" (3<p<peKT OueHI1BaeTC51 rro
pa3HOCTI1 KB AM 11 KM) rrpl1 I1HI1Ul1aUJ111 PBC I1MeeT xapaKTepHylO ,UJI5l ,UaH­
HOH Mo,UeJII1 KYIIoJI006pa3HY1O <poPMY C MaKCJ1MaJIbHbIM 3HaQeHJ1eM rrOKa3aTeJI5l
Ilpl1 orrpe,UeJIeHHOH KOHIJ;eHTpa.uJ1I1(ll5lX)/pa30BoH 'uo3e(ax), xapaI<TepI13yrolll~
Hal160JIee aKTI1BHbrM MOTI1BaIllioHHbrH 3!p<peKT coe,UI1HeHI1H. Mo,UeJIb I1HllUlla­
UI1I1 PBC Y MbIlllell rrp051BllJIa BbICOKYIO QYBcTBJ1TeJIbHOCTb 11 CeJIeKTllBHOCTb.
TaK, Ha 3TOH Mo,UeJUI B TeQeHl1e O,UHOll 3KCrrepl1MeHTaJIbHOH CeCCJ1ll BbUIBJI5l­
IOTC5I rro,UKpeIIJI5IlOllll1e CBOHCTBa He TOJIbKO 3TaJIOHHbIX a.rr.uMKTJ1BHbIX cpe,UCTB
(orrl1aTbI, KOKaI1H, aM<peTaMMH, 3<pe'upOH), HO 11 TaKMX BellleCTB, KaK 3TaHOJI,
HI1KOTI1H, KO<peJ1H. Orrl10lll[Hble aHaJIbreTI1KJ1, KOTopble JIllllleHbI Bblpa)KeHHoro
a.rr.uI1KTllBHOro rrOTeHUllaJIa (6YTop<PaHOJI, HaJI6y<pI1H, TpaManOJI), He rrp051BJI5l­
lOT rrO,UKperrJI5flOlllllX CBOHCTB Ha ,UaHHOll Mo,UeJIll.
B ra6JI. 1 cyMMllpoBaHbl cpaBHMTeJIbHble l[OCTOI1HCTBa II orpaHllQeHI15l l[aH­
HOll Mo,UeJII1. TaKMM o6pa30M, MeTO,U llHllUl1aUllM PBC y MbIllleH 5IBJI5leTC5f 'fyB­
CTBllTeJIbHbIM 11 6bICTpbIM crroco6oM OueHKM a.rr.ullKTMBHoro rrOTeHUllaJIa, Y,UOB'­
JIeTBOp51lO111llM Tpe60BaHlliIM 'rrepBllQHoro CKpllHJ1HrOBOro TeCTa.
Y CJlOBI151 H orpaHI1'lCHIUl
}lOCToHHCTBa
MeTOll
ITpcllMYlUecTBcHHO Ka'leCTBCHHall
(".na-HeT") OUCHKa pC3ynhTaToB TeCTa
npll c6anaHCHpoBaHHoi1 no I1CXOllHO­
My npCnnO'lTCHI1IO OTceKOB 3KcncpH­
MCHTanhHoll! KaMcphl npoucnypc I1C­
cnCllOBaHHil (unbiascd proccdurc)
B03MO)l(HOCTh napannCJlhHOrO Ha6nlO­
,nCHl1il 3a I1Hnl1BI1,nyanhHbIM nOBCnC­
HHCM )l(I1BOTHOro B ncpl10.nc o6ycnoB­
Hc06~O)l,I1MOCTh npOBc,neHl1il
nOnOJlHI1TCJlhHOrO I1CCJle.no­
BaHl1il no cneUl1anbHOMY
npoToKony Mil cpaBHCHHil
MOTHBaUJ10HHoi1 "ueHHOCTI1"
I1CcJ1e,llyeMorO 11 3TanoHHoro
COC,llJ1HeHI1Il
nl1BaHl1il
TCXHI1'lCCKall npOCTOTa, llCWCBH3Ha,
BblCOKail np0l13BOlll1TenhHOCTh MeTo.na
BHyTpl1BeHHOe ca­
M.OBBelleHlle: HHJ1­
UHaUl1il (MhlWI1)
TCXHI1'lCCKail npOCTOTa: I1CKJlIO'1aIOTCil
HMITJIaHTaUI151 COCYlll1CThlX KaTCTcpOB,
np Cn Ba pl1TCJlhHOC 06yqCHI1C )lGIBOT­ HhlX
ManblC 3aTpaTbi BpCMCHJ1: cpcnHllil
npOn On )l(l1TCnhHOCTb J1ccnenOBaHll51
O)l,Hoi1n0 3 bI - 1 '1, I1ccnCnOBaHHC on­
Horo coe,nI1HCHHil (nonHa51 KpHBall
".n03a-3¢¢CKT") npl1 Han 11'1 11 11 MHO­
rOKaHanhHot! yCTaHOBKl1 - 1-3 llHil.
KOHTPOJlI1PYCTCil anJ1ilHI1C llCCJlC,llYC­
Moro COC,llHHCHI151 Ha 0PI1CHTI1POB0'1­
HO-llCCJlCnOBaTCnbCKYIO pcaKuHIO
(KoHTponhHoc )l(I1BOTHoe)
BHyTpJ1BeHHOC ca­
MOBBc.neHHc: HHH­
UHaUH51 (KphIChl)
ITP51MOC ,llOKa3aTcnhCTBo nO,llKpCn­ JIlllOwcro nOBeneHHil nOI1CKa 11 no­
Tpc6ncHHil 3¢¢CKTa I1ccncnycMoro
BCWCCTBa
T a 6 n II U a
1. CpaBHHTeJlbHaJI xapaKTepBCTHKa MeTO)l,OB oueHlili a)I,)I,BKTHBHorO IIOTellllllana
MeTOll
.uOCTOHHCTBa
YCJlOBH5l H orpaHH'leHHll
3J1eKTPI1'lCCKail ca­
MOCTllMYJlllUl1il M03ra
B03MO)l(HOCTh nOBTOpHoro TecTHpoBa­
HH51 rpynnhl )l(I1BOTHhIX
B03MO)I(HOCTh OueHKI1 3aBI1CI1MOCTI1
"llo3a-3¢¢CKT" 11 "BpeM51-3¢¢eKT"
Ha" O.nHOM II TOM )l(C )l(I1BOTHOM 11
OUCHKI1 napaMeTpOB aKTHBHOCTH H
3¢¢CKTI1BHOCTI1 ¢apMaKOnOrl1'lCCKOrO
cpe.nCTBa
B03MO)l(HOCTh OUCHKH 3¢¢CKTOB no­
BTOpHOro BBc.neHHil BelUCCTB (Tonc­
paHTHOCTh, 3aBI1CHMOCTh, CeHCHTI13a­
BnaJ(CHHC MCTo.naMH cTepeo­
TaKCl1'lecKoi1 llMnJlaHTaUlll1
3neKTpo.nOB
Hanl1'me aJ(eKBaTHoi1 anna­
paTYpbl ,!lJlJl Hccne.nOBaHl1il
onepaHTHhlX pcaKUlli1 II
3neKTpOCTI1MynilUllH M03ra
06il3aTenhHocTh 3TanOB Bhl­
pa60TKH 11 cTa6Hnl13aUlll1
onepaHTHoi1 peaKUHH
B03MO)l(HOCTb oW1l6KI1 B
oueHKe 3¢¢eKTa BcweCTB
113-3a ¢apMaKorcHHoro Bnllil­
HI151 Ha BhlIIonHcHlle onc­
paHTHot! pcaKUl111 BHe CBil311
C 113MCHCHI1CM ¢YHKUI1I1 CI1C­
TeMhl "HarpaJ(hl"
Ull51)
YcnOBHOpe¢nCKTOp­
Hoe npellnO'lTCHI1C
MeCTa
3¢¢eKT coc.nI1HeHH51 OUCHllBaeTC51
nocJle ero BblBC.nCHHil H3 OpraHI13Ma
(I1CKnIO'laCTCil Henocpe.nCTBeHHOC
BnllilHlle BClUeCTBa Ha nOBe)l,eHI1C BO
BpeMil TCCTa)
BHyTpHBeHHOC ca­
MOBBcjJ.eHl1c: no,llilcp­
)l(aHI1C (KpbIChl)
.
B03MO)l(HOCTb Mi'lTeJlhHoro 113yqeHI1il
nOTpe6J1eHl1il aJ(jJ.i'lKTI1BHOro BCwccTBa
H BJ1IUlHJ151 Ha Hero ¢apMaKOJlOrl1'1C­
CKHX H I1HhlX ¢aKTOpOB
•
B03MO)l(HOCTh OUCHKl1 nOTpc6J1CHJ1il
aJ(jJ.i'lKTHBHhIX coe.nI1HeHI1i1 no Mexa­
HH3MY KaK n0J10)l(HTeJ1 bHoro, TaK 11
OTpHuaTenhHoro (y 3aBI1CI1MhlX )1(11­
BOTHhIX) nOjJ.KpCnJ1CHHil
B03MO)l(HOCTh OueHKl1 cnoc06HOCTI1
nO,llilCp)l(HBaTb caMOBBc,nCHHe jJ.pyrl1x
BelUCCTB npH 3aMCHC HMI1 HcxonHOrO
COCnI1HeHJ1il (TeCT 3aMeHbl)
3Ha'lI1TCnhHaJI Bapl1a6cnh­
HOCTb I1H)I,HBllilyanhHblx .naH­
HhlX
- 325­
- 324­
Hc06xojJ.HMOCTb COOTBeTCT­
BYlOwero annapaTHoro i'l
nporpaMMHoro 06eCne'lCHJ1il
HCB03MO)I(HOCTb MHoroKpaT­
HOro HCnOnh30BaHJ151 )l(HBOT­
HhIX Mil OUCHKI1 nO,ll,llcp)l(a­
Hl1il BHyTpl1BeHHOro caMOB­
BC,lleHI151
I1H)I,I1BI1,llyanhHall, UHpKaJ(I1­
aHHail, ynbTpaJ(l1aHHail J1 ce­
30HHall Bapl1a6cJlhHOCTh 6a­
30BOt! oncpaHTHoll! pcaKUHH
(BblrnilnhIBaHI151 B OTBCpCTHC)
Hc06xo,nI1MOCTh HMnJlaHTa­
UJ1H BHyTpl1Cocy,nl1cToro Ka­ TCTcpa
Hco6xo.nHMOCTh COOTBCTCT­
BYIOWCt! annapaTYphI 11 CI1C­
TCMbl ynpaancHl1il (oncpaHT­ HhlC KaMcphl, I1HbCKTOPhl,
npoTI1BonepcKpyql1BalOWHC
YCTpoi1cTBa H np.)
T pynocMKoCTb H CpaBHI1TCnh­ HO 60JlhWall np0,llOJl)l(I1TCJ1b­
HOCTb HCCJ1C,llOBaHH5l
To )l(C, 'ITO B CXCMC HHI1Ul1a­ UHI1
B03MO)l(HO H3MCHCHHC pcaK­ UI1I1 Ha I1CCJlCnYCMOe BeWCCT­ BO npl1 nOBTopHoi1 3KCn03J1­ UI1I1 (TOJ1CpaHTHOCTb, ceHCH­ TI13aUllil)
2. BhIpa60TKa YCJIOBHopeqlJIeKTOpHoH peaKImH npe,ll;nOqTeHHH MeCTa (YPllM)
YKphlC H mooeH
Het1:'rpaJIhHhIe 06CTaHOBOqHhIe pa3n:pa)J(JueJU! rrpl1 COqeTaHl111 C "Harpa)l([(aJo­
111I1M" 3<p<peKTOM a.n:D:I1KTI1BHhlX Cpen:CTB MOryr rrpl106peTaTh C06cTBeHHhIe "aT­
TpaKTI1BHhIe" CBOH:CTBa, Ha 6a3e KOTOphlX BhIpa6aThIBalOTc!'! I1HCTpYMeHTaJIhHhIe
peaKUl111 BTOpOro 11 60JIee BhICOK\1X rrOp!1D:KoB, KOTophIe rron:KpeIlJI!1lOTC!'! 3TI1Ml1
e JIeKT
yCJIOBHop <p
opHhIMI1 p a3n:p8JKI1TeMMI1. ECJII1 3<p<peKT a.n:D:I1KTI1BHOro Bellle­
CTBa I1CrrhIThIBaeTC!'! %MBOTHhIM B orrpen:eJIeHHOM MecTe, Harrpl1Mep B On:HOH: 113
KaMep n:Byx- HJm MHorOKaMepHOH: yCTaHOBKl1 l1JI11 y<IaCTKe "OTKphITOrO rrOM",
I1MelOllleM crreU I1 <p l1 qeCKJ1e n:I1 CKpI1MI1HaTI1BHhIe CTI1MYJIhHhIe CBOH:CTBa (TaK­
Tl1JIhHhIe, CBeTOBhIe, 060H!1TeJIhHhIe 11 T. rr.), TO %MBOTHoe rrp en:rrOql1TaeT HaxO­
n:I1ThC!'! B 3TOM MeCTe, eCJII1 eMy rrpen:OCTaBJI!1eTC!'! BhI60p. YCJIOBHope<pJIeKTOpHaR
peaKUl1!1 rrpen:rrOqTeHl1!1 MeCTa (YPITM) rrOJIyql1JIa IIIl1pOKoe pacrrpOCTpaHeHl1e
rrpl1 113y<IeHI1I1 a.n:D:I1KTI1BHhlX cpen:CTB C KOHlIa 70-x - HaqaJIa 80-x ron:OB. ECJII1
BerueCTBO rrpO!'!BJI!1eT rrpOTI1BOrrOJIO)I(HhlH: (aBepCI1BHblli) 3<p<p eKT, TO Bhlpa6aThI­
BaeTC!'! YCJIOBHope<pJIeKTopHM peaKUl1!1 1136eraHl1!1 MeCTa (YPl1M). TaKJ1M 06pa­
30M, YCJIOBHhIM pe<pJIeKC Ha MeCTO MO)l(eT I1MeTh rrpOTI1BOrrOJIO)I(HYJO HarrpaBJIeH­
HOCTh (YPITM l1JI11 YPl1M) 11 0Tp8JKaTh I1TOrOBoe B3aI1Mon:eMCTBl1e I1CCJIen:yeMo­
1'0 BellleCTBa C M03rOBhIM cy6CTpaTOM MOTl1BaUI10HHhIX peaKUI1M. BhIpa60TKa YC­
JIOBHOro pe<pJIeKCa Ha MeCTO 5IBJUIeTC5I Te)(HxqeCKI1 rrpOCThIM TeCTOM n:OKJII1Hxqe­
CKOM OueHKl1 a.n:D:I1KTI1BHoro rrOTeHUl1aJIa <papMaKOJIOrHqeCKJ1X cpen:CTB, I1MelO­
rul1M CBOI1 n:OCTOI1HCTBa 11 Hen:OCTaTKI1 (Ta6JI. 1).
MeTon:I1Ka BhIpa60TKI1 YPITM y KphIC cyrueCTByeT B n:Byx Mon:I1<pI1KaUI1!'!x:
a) C I1CXOn:HhIM rrp en:rrOqTeHl1eM )I(l1BOTHhIMI1 on:Horo 113 3KCrrepl1MeHTaJIhHhIX
OTceKOB (biased procedure).11 6) C I1CXOn:HO C6aJIaHCI1pOBaHHhIM BhI60pOM OT­
ceKOB 3KCrrepI1MeHTaJIhHOH: KaMephI (unbiased procedure). ITPI1 rrepBoM Bapl1­
aHTe MeTon:a JIerqe rrOJIyql1Th QeTJ<Y1O KPI1BYJO 3aBl1Cl1MOCTl1 "n:03a- <p<p KT",
3
e
on:HaKO rrpl1 3TOM Tpyn:HO I1CKJIIO'J:I1Th BKJIaD: aHTl1aBepCI1BHhIX CBOMCTB I1CCJIe­
n:yeMoro BerueCTBa B OKOHQaTeJIhHhIM 3<p<peKT 06YCJIOBJII1BaHl1!1. ITPI1 I1CrrOJIh­
30BaHl111 BTOPOM Mon:I1<pI1Kau·1111 yBepeHHocTh B orrpen:eJIeHI1I1 113611paTeJIhHhIX
"Harpa)I(LJ:alOruI1X" (YPITM) l1JI11 aBepCI1BHhIX (YPI1M) 3<p<p e KTOB rrpenapaToB
BhIIIIe. B HaCTo!'!ruI1X MeTon:I1'IeCKI1X peKoMeHn:aUI1!'!x paCCMaTpl1BaeTc!'! MeTo­
n:I1Ka BhIpa60TKI1 YPITM rrpl1 I1CXOn:HO C6aJIaHCI1pOBaHHoM BhI60pe OTceKOB
3KCrrepl1MeHTaJIhHOM KaMephl (unbiased procedure).
MATEPMAJIbHO-TEXHlflIECKOE OEECllEQEHIIE METOM
3KCrrepl1MeHTaJIhHhIe )I(I1BOTHhIe - KPhIchl-caMUhI MaCCOH: 150-250 r. Pe­ KOMeHn:yeTc!'! con:ep)l(aTh )I(l1BOTHhIX npl1 I1HBepTl1pOBaHHoM pe%MMe OCBellle­ Hl1!1 (12-QaCOBOM UI1KJI TeMHoTa/cBeT) D:JIJI aKTI1BaUl111 nOBen:eHl1!1 BO BpeM5I
3KCrrepl1MeHTOB B TeMHOBOM <pa3e. 3KCrrepl1MeHThI Ha'J:I1HalOT rrpl1MepHo Qepe3
qac rrOCJIe HaqaJIa TeMHOBoro UI1KJIa. ITpen:Bapl1TeJIhHO <P 0 PMI1PYJOTC!'! rpyrrrrhI
(He MeHee 8 %MBOTHhIX B rpyrrrre) M5I 113yqeHl1!1 3<p<p e KTa Ka)l(LJ:OH: n:03hI rrperra­ paTa 11 paCTBOpI1TeM.
3KCnepl1MeHTaJIhHaR YCTaHOBKa 06hIqHO COCTOI1T 113 n:Byx l1JI11 60JIee KaMep
pa3JII1QHOH: <POPMhI 11 pa3Mepa, KOTophIe OTJII1QalOTC!'! no TeKcrype nOJIa, OKpa­
CKe CTeHOK 11 T. n., QTO n03BOMeT )I(l1BOTHhIM n:11<p<pepeHUl1pOBaTh pa3HhIe Ka­
MephI. Ba)I(Ho, QT06hI npl1 CB060.!lHOM I1CCJIen:OBaHI1I1 KaMep. B rpynrre KphIC He
npO!'!BJI5IJIOCh rrpen:nO'J:TeHI1!1 On:HOH: 113 HI1X. )KeJIaTeJIhHa aBTOMaTI1QeCKa!'! pe­
rl1cTpaUl1!1 C rrOMOlllhlO MeXaHI1QeCKI1X I1JII1 OrrTI1QeCKJ1X n:aTQI1KOB BpeMeHI1 Ha­
XO)I(LJ:eHI15I )I(l1BOTHhIX B OTceKax yCTaHOBKI1 11 KOJII1QeCTBa nepexon:OB.
- 326­
OlllICAHIIE METO)l;A
ITpOTOKOJI
I1CCJIen:OBaHl1!1
rrpen:ycMaTpl1BaeT
rrepl1on:hI
06YCJl06JllUJQHUJI
11
mecmUp06QHUfl. IIepI1on: <papMaKOJIOmqeCKOrO 06yCJIOBJII1BaHl1!1 rrpon:OJI)l(aeTCH
4 n:H!1. Ka)l(LJ:hIM n:eHh rrpOBOD:!1T .!lBe ceccl1l1 BhIpa60TKl1 yc.iroBHoro pe<pJIeKCa Ha
MecTO. TIepBaR ceCCl1!1 !'!BMeTC5I n:11<p<pepeHUl1pOBOQHOM. TIepe.!l rrOMellleHl1eM B
on:I1H 113 OTceKOB (OTCeKl1 KaMephI pa3n:eJIeHhI rreperopon:KOH:) Ha 20-45 MI1H (B
38.BI1CI1MOCTI1 OT CpOKOB n:eH:CTBl1!1 rrperrapaTa) %MBOTHhIM BBOn:!'!T paCTBOpl1­
reJIh. Bo BpeM5I BTOPOH: CeCCl111 BBOD:!1T I1cCJIen:yeMoe coen:I1HeHl1e (B KOHTpOJIh­
HOH: rpyrrrre paCTBOpI1TeJIh) rrepen: rrOMellleHl1eM )I(l1BOTHOro B npOTI1BOrrO­
JIO)I(HhIH: OTceK Ha 20-45 MI1H. Pa3MellleHI1e )I(l1BOTHhlX rrOCJIe I1HbeKUl111 B TOM
MJII1 I1HOM OTceKe np0I13Bon:!'!T B CJIy<IaH:HOM rrOp!1.!lKe TaKl1M 06pa30M, qTO rro­
irOBI1Hy rpynnhI pa3MelllalOT B .n:aHHOM OTceKe rrOCJIe I1HbeKUl111 rrperrapaTa, a
.!lPyrylO rrOJIOBI1HY nOCJIe BBe.!leHl1!1 paCTBOpI1TeM. TIoCJIe Ka)l(LJ:Oro OrrhITa
KaMephI 06pa6aThIBalOT 3 % pacTBopoM rrepeKl1Cll BOn:OpOn:a.
3aK.JIK)qHTeJIhHOe TeCTl1pOBaHl1e BhIpa60TKl1 yCJIOBHOro pe<pJIeKCa Ha MecTO
lJPOBOD:!1T qepe3 72 Q rrocn"e nOCJIen:Hero 06yCJIOBJII1BaHI1!'!. l-b KaMephI BhIHI1Ma­
eTC!'! rreperopon:Ka Me)I(LJ:y OTCeKaMI1, 11 B TeqeHl1e 15 MI1H KphIChI CB060.!lHO I1C­
CJIen:YJOT 3KCnepl1MeHTaJIhHYJO KaMepy.
Perl1CTpl1pYlOT BpeM!'! HaxO)I(LJ:eHI1!1 B oTceKax 11 KOJIxqeCTBO rrepexon:OB 113 on:­
HOro OTceKa B n:pyroH:. BpeM!'!, rrpOBon:l1MOe B OTceKe, aCCOUl1l1pOBaHHOM C n:eH:­
CTBl1eM nperrapaTa, CpaBHI1BalOT CO BpeMeHeM HaxO)I(LJ:eHI1!1 B OTceKe, aCCOUI1I1PO­
BaRHOM C paCTBOpI1TeJIeM. TIOJIO)J(J1TeJIhHOe 3HaQeHl1e pa3Hocrn n:Byx BeJIl1ql1H
YKa3hIBaeT Ha BhIpa60TKY YPIIM, a OTpl1uaTeJIhHOe Ha YPI1M. B KaQeCTBe aJIh­
repHaTI1BHOrO (KBaHTOBoro) rrOKa3aTeM I1CrrOJIh3YJOT KOJIHqeCTBO )I(I1BOTHhIX B
rpynrre C BhIpa60TaHHOH: YPIIM l1JI11 YPI1M. 3a Kpl1Tepl1H: npen:rrOQTeHI1!1 YC­
JIOBHO rrpl1HI1MaeTC!'! BpeM!'! HaxO)I(LJ:eHI1!1 B n:aHHOM OTceKe 60JIee
(60JIee 600
c) l1JI11, COOTBeTCTBeHHO MeHee
(300 c) OT 06111ero BpeMeHI1 TeCTa (900 c).
3TOT Kpl1Tepl1M npl1MepHO COOTBeTCTByer n:l1arra30HY .!lOBepI1TeJIhHhIX rpaHI1U D:JI!1
)I(\1BOTHhIX KOHTpOJIhHOH: rpynrrhI, rrOJIyqalOIIIl1X 1130ToHxqeCKl1H: paCTBop.
2/3
1/3
3C1>C1>EKTIIBHOCTb IICIIOJIb30BAHI1JI METO)l;A
IIOJIO)l(I1TeJIhHhIH: YCJIOBHhIH: pe<pJIeKC Ha MeCTO, aCCOUl1l1pOBaHHoe C <pap­
MaKOJIOmQeCKI1M 3<p<peKTOM, OueHI1BaeTC5I KaK KOCBeHHoe CB\1D:eTeJIhCTBO no­
JIO)l(l1TeJIhHhIX MOTl1BaUl10HHhIX CBOH:CTB 113yqaeMoro coen:I1HeHI1!'!. MeTon: BhI­
pa60TKI1 YPIIM B paCCMOTpeHHOH: MOn:I1<pI1KaUI1I1 n:OCTaTOQHO QYBCTBI1TeJIeH 11
rr03BOMeT BhI!'!BHTh an:D:I1KTI1BHhIH: rrOTeHUl1aJI KaK "60JIhIIII1X" (KOKaHH, MOp­
<pI1H), TaK H MaJIhIX (KO<peI1H, HI1KOTI1H, 3TaHOJI) an:D:I1KTI1BHhIX cpen:CTB. OH
TaK)l(e cneUI1<pI1QeH H He BhI!1BJI!'!eT rrOJIO)l(l1TeJIhHOrO yCJIOBHOrO pe<pJIeKCa Ha
MeCTO rrpI1 COQeTaHl111 C 3TaJIOHHhIMl1 BellleCTBaMI1, He HMelOIUI1MI1 an:D:I1KTI1B­
Horo rrOTeHUl1aJIa (HeHapKOTI1QeCKl1e aHaJIhreTI1KI1, HeH:pOJIenTI1KI1 11 n:p.), T. e.
He n:aeT JIO:>KHOrrOJIO)l(I1TeJIhHhIX peaKUI1H:. BMecTe C TeM BhIpa60TKa YPIIM, ac­
COUl1l1pOBaHHoro C <papMaKOJIOmQeCKI1M 3<p<peKTOM, rrpl1 OTcyrcTBl111 rrpe.!lnoQ­
TeHI1!1 KaKOrO-JII160 113 OTceKOB 3KCrrepI1MeHTaJIhHOH: KaMephI B KOHTpOJIhHOH:
rpyrrrre (unbiased procedure) He rr03BOMeT C yBepeHHOCThlO KOJII1QeCTBeHHO
pa3n:eJII1Th HCCJIen:yeMhIe BellleCTBa rro 3<p<peKTHBHOCTI1 (MaKCI1MYMY) non:Kpen­
MlOlllero 3<p<peKTa, a TaK)l(e rrOJIy<II1Th cTa6l1JIhHhIe 11 BOCrrp0I13Bon:I1MhIe KpH­
Bhle 3aBl1Cl1MOCTl1 "n:03a-3<p<peKT".
LJ:JI5I cpaBHeHI1!1 an:D:I1KTI1BHOrO rrOTeHUl1aJIa coen:I1HeHI1H: MO)l(HO I1CrrOJIh30­
BaTh Bapl1aHT BhIpa60TKI1 YPIIM, rrpl1 KOTOpOM rrOMellleHl1e B On:I1H OTceK Ka­
MephI COQeTaeTC5I C n:eH:CTBl1eM 3TaJIOHHOrO HapKOTI1Ka (HarrpI1Mep, KOKaI1Ha), a
- 327­
B .1lpyroH - C lleticTBl1eM I1CCJIellyeMOro cOelli1HemLlI. B 3TI1X YCJIOBI1HX MO)KHo
Bl1lleTh, 'iTO )KI1BOTHhIe np ellrrO'iI1TalOT OTCeK, aCCOUl1l1pOBaHHhlti C I1HbeKIJ:11eH
KOKal1Ha rro CpaBHeHl110 C MeCTOM, rue BBO.1lI1JII1Ch, Hanpl1Mep, Ko<peI1H, Hl1KO­
TI1H l1JI11 3TaHOJI. C .llpyroi1 CTOpOHhI, )KI1BOTHhIe He OTllaJOT HBHoro npellrrO'1Te­
HI1H OTceKy, aCCOUl1l1pOBaHHOMY C KO<peI1HOM, rrepell MeCTOM, r.n:e OHI1 I1CI1hI­
ThIBaJIl1 lleticTBl1e HI1KOTI1Ha l1JI11 3TaHOJIa.
OCHOBHhIe Tpe60BaHM K yCTaHoBKe MH Bhlpa60TI<J1 YPDM y MhIWeH aiIa­
JIOr11'iHhI TaKOBhIM MH KphIC. Do cpaBHeHl110 C KphICaMI1 MhIWI1, KaK rrpaBWIo,
rrpO${BAAIOT 60JIee BhICOKyIO .n: Bl1raTeJIhHYIO aKTI1BHOCTh B KaMepe, 11 BpeMeHHaJI
aCI1MMeTpM BhIpa)KeHa cJIa6ee l1JI11 OTCYTcTByeT. D03TOMY rrpoToKoJr I1CCJIe.n:o­
BaHI1${ MO)KeT rrp e.n:ycMaTpI1BaTh rrpeTeCThI .n:JI${ OueHKI1 I1CXo.n:Horo rrpe.n:rrO'1Te­
HM OTceKOB KaMephI )f(J1BOTHhIMI1, 11 3<p<peKT rrperrapara MO)KHO OueHl1BaTh no
113MeHeHI1IO (npl1pocTy B CJIyqae YPDM) BpeMeHI1 npe6hlBaHIDr )I(J1BOTHOf9 B
.n:aHROM OTCe:Ke nOCJIe nepl1o.n:a <p apMaKOJIOrl1'1eCKOrO 06YCJIOBJII1BaHI1${. I1ccJIe­
.n:OBaHl1e MO)KeT rrpOBo.n:I1ThC${ TaK)Ke 11 rro cxeMe, 113JIO)KeHHoti BhIwe lLlffi Bhlpa­
60TKI1 yCJIOBHoti peaKIJ:1111 Ha MeCTO y KphIC.
METO,IJ:ll, PEKOMEH,nYEMbIE M.H BTOPOM cDA3bI
lICCJIE,IJ:OBAHIDI (METO,IJ:bI "YTJIYEJIEHHorO CKPlIHlIHrA")
3.
lIHHUHao;lUI H nOMep:lKaHHe peaKD;H11 BHYTPHBeHHoro caMOBBe.ueHH${ (PBC)
y KpbIC
MATEPlIAJIbHO-TEXHWIECKOE OBECllE'lJEHlIE METOM
3KCrrepl1MeHTaJIhHhIe
180-200 rp.
)K[i!.!lOTHhIe.
KPhIchI-caMUhI
JII1H1111
Wistar
MaCCOH
YCTaHoBKa. KaMephI, B KOTophIe nOMerualOT )KI1BOTHhIX, I1MelOT pa3Mep
30 x 30 x 30 CM 11 cHa6)KeHhI .n:ByM${ rre.n:aAAMI1. O.n:Ha 113 HI1X rrpl1 3aMhIKaHI111
KOHTaKTOB BKJIlO'1aeT I1HbeKTOp, a BTOpa${He06xo.n:I1Ma lLlffi KOHTpOM HeCrreUI1­
<pl1'1eCKoti orrepaHTHoti aKTI1BHOCTI1 )KI1BOTHoro. B03MO)KH0 I1CnOJIh30BaHI1e
KaMep, cHa6)KeHHhIX He rre.n:aAAMI1, a .n:BYM$i OTBepCTI1${M11 .n: l1 aMeTpoM 1,5 CM Ha
BhlCOTe 2,0 CM OT rrOJIa 11 Ha paCCTO${HI1I1 15 CM .n:pyr OT .n:pyra. B 06a oTBepCTI1${
BMOHTl1pOBaHhI I1H<ppaKpacHhIe .n:aH11KI1, CB${3aHHhIe '1epe3 I1HTep<p Mc C KOM­
e
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OTBeT Tl1na BhIrJI${.QhIBaHI1${ ${BAAeTC${ 60JIee eCTeCTBeHHhIM lLlffi KphIC, '1eM Ha­ )KaT11e Ha rre.n:aJIh, 11 BhIpa6aThIBaeTC${ 6hICTpee.
,lJ,JUf I1H<PY31111 BerueCTB I1CnOJIh3YIOT MI1Kpo.n:03aTophI C peryJIl1pyeMhIMI1 CKO­
Po.CThlO rro.n:a'1l1 paCTBopOB (OT .n:OJIeti ceKyH.QhI .n:o 10-20 c) 11 06beMoM pa30­
BhIX 11H<PY3I1ti (OT 10 110 400 MKJI/Kr). OITTI1MaJIhHbIe napaMeTphI (06'heM pa30­
Boti I1H<PY31111 11 60JIIOCHa${ .1l03a) rro.n:6I1paIOTC${ I1H.n:I1Bl1llya'lbHO lLlffi Ka)KIlOro
nperrapaTa. I1H<PY3111O cO'1eTalOT co CBeTOBhIM pa3.n:pa)KJ1TeJIeM, Cl1rHaJIl13l1pylO­
rueM 0 <papMaKOJIOrl1'1eCKOM no.n:KpeIIJIeHI1I1 I1HCTpYMeHTaJIhHOH peaKUI1I1. I1H­
<PY31111 rrp0I13BOMTC${ aBTOMaTl1'1eCKI1 B OTBer Ha BhIrAA)lhIBaHl1e B O.n:HO 113 OT­
BepCTl1ti 11JII1 B OTBeT Ha Ha)KaTl1e Ha COOTBeTCTBYlO/UYlO ne.n:aJIh. COOTBeTCTBeH­
HO, orrepaHTHhIe peaKUl111 Ha rrpOT${)KeHI1I1 cpa6aThIBaHI1${ I1HbeKTopa (OT 2 .n:o
13 C B 3aBI1CI1MOCTI1 OT MapKl1 11 Tl1rra MI1Kpo.n:03aTopa) <P 11KCI1 PYIOTC${, o.n:HaKO
He Be.n:YT K aKTI1BaUl111 I1HbeKTOpa.
,lJ,JI${ 06eCrre'1eHl1${ CBo60.n:hI nepeMerueHM )KI1BOTHhIX B 3KCrrepl1MeHTe rrpl1­
MeH${IOT WapHl1pHOe coe.n:I1HI1TeJIbHOe yCTpOticTBo ("swivel joint"), rrpe.n:yrrpe)K­
.n:alOruee rrepeKpY'1l1BaHl1e coe.n:I1HI1TeJIhHhIX Tpy60K OT KaTeTepa K I1HbeKTopy.
OllHCAHHE METOJ(A
KphIcaM rrOll o6rueti aHecTe311eti '1epe3 Hapy:lKHylO ${peMHylO. BeHy B yuIKO
,npaBoro rrpe.n:cep.n:l1${ I1MIIJIaHTI1PYlOT Cl1JIl1KOHOBhIe KaTeTepbI, KOTophIe <pI1K­
cUPYIOT Ha 'ieperre )KI1BOTHOro aKpl1JIOBhIM ueMeHTOM. Qepe3 3-4 CYT rrOCJIe
orrepaUl111 KpbIC rrepeBo.n:${T B BI1Bapl1ti C I1HBepTl1pOBaHHhIM CBeTOBhIM pe)Kl1­
MOM 11 11M orpaHI1'iI1BaIOT rrl1rueBoti paUI10H C ueJIhlO CHJ1)KeHI1${ MaCCbI Ha lO­
IS % OT I1CXO.n:HOti. Qepe3 3 .n:H$i rrOCJIe 3Toro rrpl1cTyrralOT K BhIpa60TKe PBC.
tlepe.n: Ha'1aJIOM TeCTl1pOBaHI1${ rrpoBepHIOTrrpoxo.n:I1MOCTh KaTeTepa rrYTeM BBe­
lleHM 0,1-0,2 MJI 1130TOHI1'1eCKOrO COJIeBOrO pacTBopa.
ITpOTOKOJI OnhITa rrpe.n:ycMaTpI1BaeT rroBTopHbI'e e)Ke.n:HeBHbIe rrOCMKI1 )KJ1­
BOTH oro B 3KCrrepI1MeHTa.mSHYlO KaMepy 11 perl1CTpaUl11O KOJII1'ieCTBa orrepaHT­
HbIX peaKUl1ti 3a BpeM$i 3KCrrep11MeHTa. ITpaKTl1'1eCKI1 y.n:06Hee I1CrrOJIb30BaTb
'orpaHl1'1eHHylO BO BpeMeHI1 ceCC1110 PBC (1-3 '1). 3a.n:a'1l1 I1CCJIe.n:OBaHM orr­
pe.n:eMIOT rrOBTopHOCTb 11 peryAApHoCTh ceccl1ti. ITPI1 BbIpa60TKe PBC 06bl'iHO
K lI$iToti ceCC1111 BhffiCH5feTC${, crroco6HO JII1 )KI1BOTHOe o6yql1TbCH PBC rrpl1 113­
6paHHoti pa30Boti .n:03e I1CCJIe.n:yeMoro coe.n:I1HeHM. PeKOMeH.n:YeTC${ I1ccJIe.n:o­
BaTb HeCKOJIbKO pa30BblX .n:03 (He MeHee 4-5)113yqaeMOrO coe.n:I1HeHM.
IToKa3aTeJI${MI1 PBC ${BMIOTC${ KOJIl1'1eCTBO caMoBBe.n:eHI1M rrperrapaTa B Ka­
)KllbIti 113 TeCTOBbIX llHeti, a TaK)Ke KOJIl1'1eCTBO BbIrAAJlhlBaHl1ti B HeaKTI1BHOe
OTBepCTl1e (11JI11 Ha)KaTI1H Ha "HeaKTI1BHYlO" rre.n:aJIb). Perl1CTpl1pYIOT TaK)Ke CyM­
MapHylO .n:03Y BerueCTBa, BBe.n:eHHylO 3a ceCCI1IO. B CJIyqae I1CrrOJIh30BaHM npo­
mOKolla 6blpa6omKU PBC rrOCJIe OKOH'1aHI1${ 3KCrrepl1MeHTa (5 .n:HeM) )KJ1BOTHbIX
3a611BalOT 11 nOJIO)KeHl1e BHYTpI1BeHHoti KaHIOJII1 Bepl1<pI1UI1PYlOT rI1CTOJIOrl1'1e­
CKI1. B omITax C noOOepJICaHUeM PBC rrOCJIe rrepl1o.n:a TpeHl1pOBKI1 (5-8 .n:Heti)
60JIbllll1HCTBO )I(l1BOTHbIX (60-70 %) 06yqaeTC${ caMOBBe.n:eHI1IO 3TaJIOHHbIX
11I1KTI1BHbLX coe.n:I1HeHl1ti (KOKaI1Ha, MOP<pI1Ha, 3TaHOJIa). B .n:aJIbHetiWI1X orrbl­
Tax I1CrrOJIb3YlOT TOJIbKO )KI1BOTHbIX co cTa611JIbHhIM ypoBHeM rrOTpe6JIeHI1${ 3Ta­
JIOHHOrO a.n:.QI1KTI1BHOrO rrperrapaTa (KoJIe6aHI1${ He 60JIee 15 % OT cpellHero
ypOBH5f Ha rrpOT${)I(eHI1I1 3 rrOCJIe.n:OBaTeJIbHbIX 3KCrrepl1MeHTaJIbHbIX ceccl1i1).
a.n:­
3cDcDEKTlIBHOCTb MCnOJIb30BAHM.H METOM
PBC Y KpblC I1CrrOJIb3yeTC${ llAA rrpe.n:CKa3aI;l.11${ a.n:.QI1KTI1BHOrO rrOTeHUl1aJIa
<p113I10JIOrl1'1eCKI1 aKTI1BHbIX coe.n:I1HeHl1ti rrO'1TI1 COpOK JIeT. Mo.n:eJIb rro.n:TBep­
.n:l1JIa CBOIO '1YBcTBI1TeJIbHOCTb 11 crreUI1<pI1'1HOCTb. C ee rroMorublO BbffiBJI${IOTC${
rro.n:KpeIlAAlOru11e cBoticTBa rrpaKTl1'1eCKI1 Bcex rrCI1XOaKTI1BHblX coe.n:I1HeHI1M,
KOTopbIe 113BeCTHbI CBOI1M a.n:.QI1KTI1BHbIM rrOTeHUl1aJIOM y '1eJIOBeKa. CooTBeTcT­
BeHHo, BerueCTBa, He ${BAAlOrul1eC${ 06beKTOM 3JIoyrroTpe6JIeHI1${ y '1eJIOBeKa, He
rrOMep)f(I1BaIOT PBC y KpblC.
B Ta6JI. 1 cyMMl1poBaHbI CpaBHI1TeJIbHbIe .n:OCTOI1HCTBa 11 orpaHI1'ieHI1${ llaH­
Hoti Mo.n:eJII1.
4.
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AKTI1BaUI1${ peaKUl111 caMOCTI1MYAAUl111 (PCC) rrpl1 BBe.n:eHI1I1 a.n:.QI1KTI1BHOro
BeruecTBa HBJl${eTC${ HeOTbeMJIeMblM 3BeHOM .n:OKa3aTeJIbCTB e.n:I1Hoti MI1111eHI1
.n:M 3JIeKTpI1'1eCKoti (PCC) 11 <papMaKOJIOm'ieCKoti (I1cCJIe.n:yeMoe BeruecTBo)
CTI1MYAAUI1I1 11 paCCMaTpI1BaeTC${ KaK 3KCrrepl1MeHT3..JlbHblti 3KBI1BalleHT 3H<p0­
Pl13I1pYlOruero lleticTBI1${ <papMaKOJIOrl1'1ecKI1X BerueCTB.
CyrueCTByeT 60JIblllOe KOJIl1'1eCTBO MO.n:I1<pI1KaUl1ti MeTo.n:a 3JIeKTpI1'1eCKoro
- 328­
- 329­
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caMopa3,upa)l(eHlliI M03ra, OCHOBaHHbIX KaK Ha OC06eHHOCTHX OrrepaHTHOrO
(I1HCTpYMeHTaJIbHoro) rroBeileHlliI, TaK 11 Ha Tpe60BaHlliIX, ill1KTyeMbIx He06xo­
,uI1MOCTblO I1CCJIe,uOBaHlliI KOHKpeTHOrO ¢apMaKOJIOrl1'-IeCKOrO areHTa. HeCMOT­
pH Ha MHOro06pa311e 9KCrrepl1MeHTaJIbHbLX rrO,uXO,uOB, JJ:JIl1 06bI'lHbLX CKPI1HI1H­
rOBbIX ueJIefi rrpl1 I1CCJIe,uOBaHI1I1 a.u.uI1KTI1BHOrO rrOTeHUl1aJIa ¢apMaKOJIOrl1'le­
CKI1X areHTOB C rrOMOWblO PCC Hal160JIee YlH¢OpMaTI1BHbIM 11 KOppeKTHbIM
rrpH3HaHO I1CrrOJIb30BaHHe MeTO,uI1K, rr03BOMIOWl1X OueHHBaTh B036y,uHMOCTh
HepBHOrO cy6CTpaTa CI1CTeMhI "Harpa,ubI" rro MI1HI1MaJIbHofi (rroporoBofl) I1H­
TeHCI1BHOCTI1 "H arpa)l()lalO!llefi " CTI1MyMUHI1, ,uocTaTO'lHOfi lLJIH rrOllll:ep)l(aHlliI
YCJIOBHOfi I1HcTpYMeHTaJIbHOfi peaKUI1I1.
CywecTBYIOT ,uBe OCHOBHhIe MeTo,uI1KI1 orrpe,ueJIeHlliI rroporoBofi I1HTeHCI1B­
HOCTI1 CTHMyJIHUl111 ("TI1TpOBaHl1e rropora"): "ayToTI1TpoBaHl1e", rrpl1 KOTOpOM
rrOpOrOBaH I1HTeHCI1BHOCTh KOHTpOJIl1pyeTcH CaMI1M )l(I1BOTHhIM, 11 TI1TpoBaHl1e
rropora, KOTopoe rrp0I13Bo,uI1TCH rro orrpe,ueJIeHHoMy aJIrOpl1TMy I1CCJIe,uOBaTe­
JIeM. HecMOTpH Ha I1CKJIIO'lI1TeJIhHYIO 06beKTHBHoCTh MeTOill1K11 "ayTOTI1TpOBa­
HIDl", ee rrpaKTI1'leCKOe HCrrOJIh30BaHHe corrpl1)l(eHO CO 3Ha'lHTeJIhHbIMM 3aTpa­
TaMI1 BpeMeHH 11 pecypcoB 11 He MO)l(eT 6hITh 1136paHO L(.JUI CKpl1HI1Hra ¢apMa­
KOJIOrl1'ieCKI1X areHTOB. II09TOMY peKOMeHilyeTcH I1CrrOJIh30BaTh MeTo,uHKY TYIT­
pOBaHHl1 rropora PCC; KOTopoe ocywecTBMeT I1CCJIeilOBaTeJIh.
MATEPlIAJIbHO-TEXHlflIECKOE OEECTIE"lJEHME METO,UA
OrrhITbI rrpOBo,uHTCH Ha caMuax KphIC Maccofl 150-300 r B 3aBI1CI1MOCTI1 01'
HCrrOJIb3yeMoro aTJIaCa M03ra KphIC. PCC I1CCJIeilYIOT B CTaHJJ:apTHoi1 KaMepe
CKI1HHepa, 060pYiloBaHHoi1" ilByrvur - "Harpa)l(JJ:alOwei1" 11 "HeHarpa)l(JJ:alOwei1",
rre,uaMMI1. ,IJ,M PCC He06xOill1M I1CTO'lHI1K 3JIeKTpI1'leCKI1X I1MrrYJIhCOB (Ha­
rrpl1Mep, CTI1MyMTOp 3C-51), KOTOphIfi rr03BOJIHeT ocywecTBMTh CTI1MYMUHIO
rro rrOCToHHHOMy TOKY B WHpOKOM aMIIJII1TYilHOM 11/11JI11 'laCTOTHOM ill1arra30He.
OTIMCAHME METO,UA
3JIeKTpOilhI I1MrrJIaHTI1PYlOT rro cTepeOTaKCI1'leCKI1M KOOPilHHaTaM B Meill1­
aJIhHhIi1 rrepe,uHeM03roBoi1 n:yqOK I1JII1 BeHTpaJIhHylO TerMeHTaJIbHYIO 06JIaCTh
(BeHTpaJIhHaH rroKphIwKa) cpeilHero M03ra. I1MIIJIaHTaUH51 ::meKTpo,uOB B BeH­
TpaJIbHYIO TerMeHTaJIhHYIO 06JIacTb peKoMeHilyeTcH B CBH311 C HI13K0i1 BepoHT­
HOCThlO B03HI1KHOBeHHl1 aBepcHBHhIX peaKUHi1 rrpH 3JIeKTpI1'leCKOM pa3ilp1l)[(e­
HHI1 ::nOM CTpyKTyphI. MoryT I1CrrOJIh30BaTbCH MOHO- I1JII1 611rrOJIHpHbIe 3JIeK­
TpOilhI. IIocJIenHl1e rrpeilrrO'lTI1TeJIhHhI 113-3a 60JIee BhICOKOM CeJIeKTI1BHOCTI1
cTHMyMUHI1. IIpl1 I1CrrOJIh30BaHHI1 MOHorroAApHhIX 3JIeKTpoiloB yCTaHaBm'lBalOT
,uorrOJIHI1TeJIbHhIi1 I1HilI1¢¢epeHTHhIM 9JIeKTpoil B HeCKB03HOM oTBepCTl111 B
JI06HOM KOCTH.
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UI1I1 PCC rrpl1 cJIe,uYIO!lll1x rrapaMeTpax pa3ilpa)l(eHI1H: rrpHMoyroJIhHbIe 6l1rro­
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,uOJI)l(I1TeJIbHOCTh cepl1l1 I1MrrYJIhCOB 300 MC, aMrrJII1TYila HMrryJIhCOB B npl1Mep­
HOM ,ul1arra30He 70- 300 MKAJJ:JIH MOHorroMpHoM CTI1MYJIHUI1I1 I1JII1 10-100
MKA lLJIH 611rrOJIHpHOM CTHMyJIHUI1I1. BhIpa60TKa peaKUHI1 PCC OCY!lleCTBJIH­
eTCH C nOMowhlO MeTo,uOB "rrOCJIe,uoBaTeJIhHOrO npI16JII1)l(eHI1H" K He06xonl1­
MOM rrOBeileH'leCKOM peaKUl111 (HanpI1Mep, Ha)l(aTHe Ha rreilaJIh). IIocJIe nOMe­
weHI1H )l(I1BOTHOro B orrepaHTHylO KaMepy rrOCJIeilOBaTeJIhHO rrOilKpenJIHIOT
"Harpa)l(JJ:aIOWeM" CTI1MYMUl1eM CHat:[aJIa HaXO)l(.fieHl1e B t:[aCTI1 KaMepbI, Hal1­
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60JIee 6JIH3KOM K "rroilKperrJIHlOwetl:" rrenaJIl1, 3aTeM Ka)l(.fioe ilBI1)l(eHl1e rro Ha­
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npaBlIeHHIO K neilaJIl1, I1CCJIenOBaHl1e rrenaJ1H' KacaHl1e neilaJll1, 11 T. il. IIocJIe
Bhlpa60TKI1 HaBhIKa Ha)l(aTI1H Ha rre,uaJIb (1-2 cecclm), Ha rrpOTH)l(eH\o[J1 3-4
e)l(eilHeBHhIX ceccl1f1 OnpeileJIHIOT aMIIJII1TYilY CTHMyJIHUI1I1, KOTopaH rro)l)lep-'
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BI1JIO, rrpl1 y,ua'lHOM I1MrrJIaHTaUl111 9JIeKTpoilo B Ha BhIpa60TKY 11 CTa611JI113a­
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40 MHH.
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mil1Tyn I1JII1 qaCTOTe I1MrrYJIhCoB). B nepBoM cJIyt:[ae I1HTeHCI1BHOCTh CTI1MYJIH­
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AAUI1I1 BBOill1TCH ¢apMaKOJIO[J1t:[ecKoe cpeilcTBo. IIpl1 He06xOill1MOCTI1 I1CCJIeilO­
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Ka 9KCnepl1MeHTaJIhHOH ceCCI1I1. IIPH paC'leTe cpeilHe9¢¢eKTI1BHbIX il03 ¢ap­
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