Methamphetamine amagwira ntchito yambiri ya machitidwe a chiwerewere pa makoswe amphongo (2010)

Neuroscience. 2010 Mar 31; 166 (3): 771-84. yani: 10.1016 / j.neuroscience.2009.12.070. Epub 2010 Jan 4.

Frohmader KS, Wiskerke J, RA wanzeru, Lehman MN, Coolen LM.

gwero

Dipatimenti ya Anatomy ndi Biology ya Cell, Schulich School of Medicine ndi Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1.

Kudalirika

Methamphetamine (Meth) ndizovuta kwambiri. Kugwiritsa ntchito mankhwala osokoneza bongo nthawi zambiri kumagwirizanitsidwa ndi chizoloŵezi cha chiopsezo cha chiwerewere ndi kuwonjezeka kwa chiwerengero cha anthu omwe ali ndi kachilombo ka HIV ndi mauthenga omwe amachititsa kuti anthu azikhala ndi chilakolako chogonana, kukondweretsa, ndi kugonana. Zomwe zimapangidwira zokhudzana ndi kugonana kosokoneza bongo sizidziwika. Kafukufuku wamakono akuwonetsa kuti kayendedwe ka Meth mu makoswe aamuna amachititsa neurons m'madera a ubongo a masolimbic dongosolo lomwe likukhudzidwa ndi lamulo la chiwerewere. Mwachindunji, Meth ndi mating amagwiritsa ntchito maselo pamtundu wa accumuls core ndi shell, basolateral amygdala, ndi anterior cingulate kalotex. Zotsatirazi zikuwonetsa kuti mosiyana ndi chikhulupiliro cha masiku ano, mankhwala osokoneza bongo angayambitse maselo omwewo monga chiwongolero cha chilengedwe, ndiko khalidwe la chiwerewere, ndipo amachititsa chidwi kufunafuna mphotho iyi.

Keywords: nucleus accumbens, amolgalaal amygdala, prefrontal cortex, kugwiritsa ntchito mankhwala osokoneza bongo, kubereka, kusokoneza bongo

Chilimbikitso ndi mphotho zimayang'aniridwa ndi mapulogalamu a masolimbic, malo ogwirizanitsa a m'magulu a ubongo omwe ali ndi ventral tegmental area (VTA) nucleus accumbens (NAc), amygdala omwe amachokera kumbali, ndi ammgal (corpx).Kelley, 2004, Kalivas ndi Volkow, 2005). Pali umboni wochuluka wakuti mawonekedwe a masolimbic amavomerezedwa poyang'ana ku zinthu zonse zozunza (Di Chiara ndi Imperato, 1988, Chang et al., 1997, Ranaldi et al., 1999) komanso khalidwe lopindulitsa monga chikhalidwe cha kugonana (Fiorino et al., 1997, Balfour et al., 2004). Khalidwe lachiwerewere lachiwerewere, makamaka makamaka kutsegula, limapindulitsa kwambiri komanso limalimbikitsa zinyama (Pfaus et al., 2001). Makoswe a amuna amakhala ndi malo okonda malo (CPP) kuti agwirizane (Agmo ndi Berenfeld, 1990, Martinez ndi Paredes, 2001, Tenk, 2008), ndipo adzachita ntchito zogwira ntchito kuti apeze akazi opatsirana pogonana (Everitt et al., 1987, Everitt ndi Stacey, 1987). Mankhwala osokoneza bongo akupindulitsanso komanso kulimbikitsa, ndipo zinyama ziphunzira kudzipangira zokhazokha, kuphatikizapo opiates, chikonga, mowa, ndi psychostimulants (Wanzeru, 1996, Pierce ndi Kumaresan, 2006, Feltenstein ndi See, 2008). Ngakhale zimadziwika kuti mankhwala osokoneza bongo komanso khalidwe la chiwerewere amachititsa kuti ubongo ukhale m'malo, panopa sadziwa ngati mankhwala osokoneza bongo amagwiritsa ntchito neurons yomwe imayambitsa chiwerewere.

Kafukufuku wa electrophysiological asonyeza kuti chakudya ndi cocaine zonse zimayambitsa neurons mu NAC. Komabe, othandizira awiriwa sagwiritsa ntchito maselo omwewo mkati mwa NAC (Carelli et al., 2000, Carelli ndi Wondolowski, 2003). Kuwonjezera apo, chakudya ndi kudya mankhwala osokoneza bongo sizimayambitsa kusintha kwa nthawi yaitali kwa electrophysiological monga momwe zimayambira ndi cocaine (Chen et al., 2008). Mosiyana, umboni wochuluka umasonyeza kuti khalidwe lachiwerewere lachiwerewere ndi mankhwala osokoneza bongo angagwire ntchito yomweyo m'masolimbic neurons. Psychostimulants ndi opioids amasintha malingaliro a chiwerewere mu makoswe amphongo (Mitchell ndi Stewart, 1990, Fiorino ndi Phillips, 1999a, Fiorino ndi Phillips, 1999b). Deta yaposachedwa kuchokera ku labu inasonyeza kuti zochitika zogonana zimasintha kuyankha kwa psychostimulants monga zowonetsera ndi mayankho ogwira mtima ogwira ntchito komanso kuwonetsa mphoto kwa d-amphetamine mu nyama zogonana (Pitchers et al., 2009). Yankho lofananalo lakhala likuwonetsedwa mobwerezabwereza ndi amphetamine kapena mankhwala ena ozunza (Lett, 1989, Shippenberg ndi Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren ndi Kalivas, 2000). Zonsezi, zotsatiridwazi zikusonyeza kuti khalidwe la kugonana ndi mayankho a mankhwala osokoneza bongo amatsutsana ndi neuroni zomwezo mu dongosolo la masolimbic. Choncho, cholinga choyamba cha phunziroli ndi kufufuza njira zogwiritsira ntchito neural activation ya masolimbic system ndi khalidwe la chiwerewere ndi mankhwala osokoneza bongo m'thupi lomwelo. Makamaka, ife tinayesa lingaliro lakuti psychostimulant, methamphetamine (Meth), imachita mwachindunji pa ma neuroni omwe nthawizonse amalimbikitsa khalidwe la kugonana.

Meth ndi imodzi mwa mankhwala osokoneza bongo kwambiri padziko lonse (NIDA, 2006, Ellkashef et al., 2008) ndiNdimagwirizanitsidwa kawirikawiri ndi khalidwe losinthira. Chochititsa chidwi, kuti abasebenzisi a Meth amanenetsa kuti chilakolako cha kugonana chikhale chokwanira komanso kuti chikhale chokondweretsa, komanso chikhale chokondweretsa kugonana (Semple et al., 2002, Schilder et al., 2005). Komanso, Kugwiritsa ntchito mankhwala osokoneza bongo nthawi zambiri kumagwirizanitsa ndi chiwerewere (Rawson et al., 2002). Ogwiritsa ntchito nthawi zambiri amanena kuti ali ndi zibwenzi zambiri zogonana ndipo sagwiritsa ntchito chitetezo kusiyana ndi ena ogwiritsira ntchito mankhwala osokoneza bongo (Somlai et al., 2003, Springer et al., 2007). Mwamwayi, maphunziro omwe amasonyeza kuti Meth amagwiritsa ntchito ngati chiwonetsero cha chiopsezo cha kugonana amakhala ochepa pamene akudalira zozizwitsa zosadziwika (Elifson et al., 2006). Choncho, kufufuza m'magulu a machitidwe a kusintha kwa Meth kusinthika kwa chiwerewere muzitsanzo za zinyama kumafunika kuti mumvetsetse vutoli lovuta kugonana ndi mankhwala osokoneza bongo.

Malinga ndi zomwe tatchulazi zikusonyeza kuti kumwa mankhwala osokoneza bongo, makamaka Meth, kungagwiritse ntchito ma neuroni omwe amagwiritsidwa ntchito pophatikizapo chiwerewere, cholinga cha phunziro lino ndi kufufuza njira zowonongeka ndi khalidwe la kugonana ndi kayendetsedwe ka psychostimulant Meth. Phunziroli linayambitsa njira zogwiritsira ntchito mankhwala, pogwiritsa ntchito maonekedwe a immunohistochemical a majeremusi oyambirira a Fos ndi phosphorylated Mapa Kinase (pERK) kuti azindikire kuchitapo kanthu kwachitsulo ndi khalidwe la chiwerewere ndi Meth moyenera. Fos imangowonekera mkati mwa maselo a maselo, okhala ndi mawonekedwe akuluakulu a 30-90 maminiti atatha kuyambitsa khungu. Pali umboni wochuluka wakuti kugonana kumapangitsa kufotokozera Fos mu ubongo (Pfaus ndi Heeb, 1997, Veening ndi Coolen, 1998), kuphatikizapo mesocorticolimbic system (Robertson et al., 1991, Balfour et al., 2004). Palinso umboni wakuti mankhwala osokoneza bongo amachititsa kuti PERK iwonongeke mu dongosolo la mesocorticolimbic (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). Mosiyana ndi kufotokozera kwa Fos, phosphorylation ya ERK ndi njira yamphamvu kwambiri ndipo imapezeka kokha 5-20 maminiti atatha kuyambitsidwa kwa neuronal. Mafotokozedwe apadera a Fos ndi PERK amawapangitsa kukhala zizindikiro zabwino zowonjezereka kwa neuronal ndi zosiyana ziwiri.

NJIRA ZOFUNIKA KWAMBIRI

Ophunzira

Amuna akuluakulu a Sprague Dawley (210-225 g) omwe adalandira kuchokera ku Charles River Laboratories (Montreal, QC, Canada) adagwiritsidwa ntchito pa khola limodzi lokhala ndi malo osungirako zipatala. Chipinda chamoyo chinasungidwa pa 12 / 12 h kutembenuka kwa kuwala (kuyatsa pa 10.00 h). Chakudya ndi madzi zinalipo ad libitum. Kuyesedwa konse kunkachitika pakatikati pa gawo loyamba la mdima pansi pa kuwala kofiira. Stimulus azimayi omwe amagwiritsidwa ntchito pa chiwerewere anali ovomerezeka m'magulu mwachangu kwambiri (13 mg / kg ketamine ndi 87 mg / kg xylazine) ndipo analandira mankhwala osokoneza bongo omwe ali ndi 5% estradiol benzoate (EB) ndi 95% cholesterol. Kugonana kunayambitsidwa ndi subcutaneous (sc) kuyendetsa kwa 500 μg progesterone mu 0.1 ml seame mafuta 4 h musanayesedwe. Ndondomeko zonse zinavomerezedwa ndi Komiti Yodyetsera Zanyama ku Yunivesite ya Western Ontario ndipo ikutsatira ndondomeko zomwe tafotokoza za Canadian Council on Animal Care.

Zojambula Zoganizira

Zizindikiro 1 ndi 2: Amphaka amphongo (n = 37) amaloledwa kukwatirana ndi mkazi wokonda kulandira (E) kapena kwa 30 min, yomwe inayamba kufika koyambirira muzitsulo zoyesera (60 × 45 × 50 masentimita) kawiri kawiri -yese yesetsani kuyesayesa, kuti mupeze zochitika zogonana. Pakati pa magawo awiri omaliza, magawo onse oyenerera a kugonana analembedwa, kuphatikizapo: mount latency (ML; nthawi kuyambira kufotokozedwa kwa mkazi mpaka pawuni yoyamba), latency latency (IL; kupititsa kumadzi, kuthamanga kwapakati, kutuluka kwa nthawi yoyamba (PEI; nthawi yolowera kupita kumalo oyamba), chiwerengero cha mapulogalamu (M), ndi chiwerengero cha intromissions (IM) (Agmo, 1997). Amuna onse amalandira 1 ml / kg jekeseni tsiku ndi tsiku kwa 0.9% NaCl (saline; sc) 3 masiku otsatizana asanafike tsiku loyesera, chifukwa chozoloŵera kulandira ndi kulandira. Tsiku lina tsiku lisanayambe, amuna onse anali osakwatira. Amuna amodzi, Fos ikhoza kusokonezedwa ndi zikhalidwe zomwe zimagwirizanitsidwa ndi kugonana koyambirira (Balfour et al, 2004). Choncho, zonse zomwe zimayesetseratu ndikuyesa kuyendetsa poyesa kumapeto kwa mayesero omaliza anachitidwa pakhomo lapakhomo (kupeŵa zifukwa zowonongeka) kuti zisawonongeke zowonongeka zomwe zimapangitsa kuti anthu asamayende bwino. Amuna adagawidwa m'magulu asanu ndi atatu oyesera omwe sanagwirizane ndi chiwerewere pazochitika ziwiri zoyambirira zokambirana (deta yosasonyezedwe). Pachiyeso chomaliza, abambo amaloledwa kukwatirana mu khola lawo mpaka atawonetsa kukondana (kugonana) kapena sanalandire mkazi wokondedwa (palibe kugonana). Amuna onse osungunuka adapangidwanso maminiti a 60 pamayambiriro amayamba kusinthana kuti athandizire kufotokozera kwa Fos. Amuna amalandira jekeseni wa 4 mg / kg Meth kapena 1 ml / kg saline (sc) (n = 4 aliyense), 10 (kuyesera 1) kapena 15 (kuyesera 2) miniti isanayambe kusungunula, pofufuza za fosphorylation MAP kinase. Mlingo ndi nthawi isanakhale kusakaniza zinachokera ku malipoti apitayi (Choe et al., 2002, Choe ndi Wang, 2002, Chen ndi Chen, 2004, Mizoguchi ndi al., 2004, Ishikawa et al., 2006). Magulu otsogolera ankaphatikizapo amuna omwe sanakwatirane, koma analandira Meth 10 (n = 7) kapena 15 (n = 5) min isanafike nsembe, kapena injini ya saline 10 (n = 5) kapena 15 (n = 4) min isanafike nsembe . Potsatira nsembe, ubongo unasinthidwa kuti ukhale ndi immunohistochemistry.

Yesetsani 3: Popeza kuti Meth yapamwamba imagwiritsidwa ntchito poyesa 1 ndi 2, kuyesa kwina kwapadera kunayesedwa kuti afotokoze ngati khalidwe la kugonana ndi mlingo wa kuchepa wa Meth umapangitsa miyambo yodalirika yothandizana ndi neural activation. Phunziroli linayendetsedwa mofanana ndi kuyesera 1 ndi 2. Komabe, pamayesero omalizira, magulu osakanikirana ndi osasamala (n = 6 aliyense) analandira 1 mg / kg Mph (sc) 15 min asanapereke nsembe.

Yesetsani 4: Kuti muyese ngati neural activation yochitidwa ndi kugonana ndi Meth ndi enieni kwa Meth, kuyeserayi anafufuza ngati zofanana mapulogalamu neural activation activation angakhoze kuwona ndi psychostimulant d-amphetamine (Amph). Kuyesera uku kunayendetsedwa mofanana ndi kuyesera 1 ndi 2. Komabe, pamayesero omaliza, amuna amathandizidwa kukhala Amph (5 mg / kg) kapena saline (1 mg / kg) (sc) 15 min asanapereke nsembe (n = 5 aliyense). Kulamulira amuna osadziwika amalandira saline kapena Amph 15 maminiti asanapereke nsembe. Zowonongeka za magulu oyesera omwe agwiritsidwa ntchito mu kuyesera 1-4 imaperekedwa Gulu 1.

Gulu 1      

Zowonongeka za magulu oyesera anaphatikizapo kuyesera 1-4.

Kukonzekera Minofu

Nyama zinkasakanizidwa ndi pentobarbital (270 mg / kg; ip) ndipo zimagwiritsidwa ntchito mopangidwa ndi transcardially ndi 5 ml wa saline, kenako ndi 500 ml 4% paraformaldehyde mu 0.1 M phosphate buffer (PB). Ubongo unachotsedweratu ndikupangidwira kwa 1 h kutentha komweko, kenako kumizidwa mu 20% sucrose ndi 0.01% Sodium Azide mu 0.1 M PB ndipo amasungidwa ku 4 ° C. Chigawo cha Coronal (35 μm) chinadulidwa pa microtome (H400R, Micron, Germany), chinagwiritsidwa ntchito pazinthu zinayi zofanana mu cryoprotectant solution (30% sucrose ndi 30% ethylene glycol mu 0.1 M PB) ndipo yosungidwa ku 20 ° C mpaka processing.

Immunohistochemistry

Zitsulo zonsezi zinkachitidwa kutentha kutentha. Zigawo zoyandama zaulere zidatsukidwa kwambiri ndi mchere wa 0.1 M wa Phosphate (PBS) pakati pa makina. Zigawo zinayambika mu 1% H2O2 kwa 10 min, kenaka atatsekedwa ndi mankhwala otsekemera (PBS okhala ndi 0.1% serum albumin ndi 0.4% Triton X-100) ya 1 h.

PERK / Fos

Pulogalamuyi imapangidwira usiku umodzi ndi mankhwala a kalulu polyclonal motsutsana ndi p42 ndi mapu a p44 amphindi ERK1 ndi ERK2 (pERK; 1: 400 kuyesera 1 lot 19; 1: 4.000 kuyesera 2 ndi 3 lot 21; Cat Signaling Cat # 9101;), wotsatira ndi 1 h kumayambitsa matendawa ndi abulu anti-rabbit IgG (1: 500; Jackson Immunoresearch Laboratories, West Grove, PA) ndi abidin-horseradish peroxidase complex (ABC Elite; 1: 1000; Vector Laboratories, Burlingame, CA). Kenaka, minofuyi inkakumbidwa chifukwa cha 10 min ndi biotinylated tyramide (BT; 1: 250 mu PBS + 0.003% H2O2; Chizindikiro cha Tyramid Signal Amplification Kit, Life Sciences, Boston, MA) ndi 30 min ndi Alexa 488 conjugated strepavidin (1: 100; Jackson Immunoresearch Laboratories, West Grove, PA). Pambuyo pake, minofu inkapangidwanso ndi anti-polyclonal wodwala a kalulu motsutsana ndi c-Fos (1: 500; SC-52; Santa Cruz Biotechnology, Santa Cruz, CA), wotsatiridwa ndi 30 min kuphatikizapo mbuzi anti-rabbit Alexa 555 (1: 200; Jackson Immunoresearch Laboratories, West Grove, PA). Pambuyo pake, zigawozo zinatsukidwa bwino mu 0.1 M PB, zitakwera pazithunzi za magalasi ndi 0.3% gelatin mu ddH20 ndipo yophimbidwa ndi sing'anga yamadzimadzi (Gelvatol) yomwe imakhala ndi 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Kuteteza kwa immunohistochemical kumaphatikizapo kutayika kwa mankhwalawa kapena mabungwe onse awiri oyambirira, motero kusayika malemba kumalo oyenerera.

Kusanthula Deta

Chiwerewere

Pa zowonongeka zinayi, magawo oyenerera a kugonana amalembedwa monga momwe tafotokozera pamwambapa ndi kufufuza pogwiritsa ntchito kusanthula kusiyana (ANOVA). Kusanthula kwa chidziwitso cha chiwerewere patsiku lomaliza la chiwonetsero sikunatuluke kusiyana kwakukulu pakati pa magulu pazochitika zonse za kugonana.

PERK / Fos Cell Counts

Maselo osakwatiwa ndi awiri omwe amalembedwa kuti Fos ndi pERK anawerengedwa m'magulu a NAc pakati ndi zigawo za shell, basolateral amygdala (BLA), amygdala apakati (MEApd), central amygdala (CeA) Pakati pa bedi la stria terminalis (BNSTpm ndi BNSTpl), ndi malo ozungulira (ACA), prelimbic (PL), ndi infralimbic (IL) madera a mPFC. Zithunzi zinagwidwa pogwiritsa ntchito kakompyuta yotentha ya CCD (Microfire, Optronics) yomwe ili pamakina a microscope Leica (DM500B, Leica Microsystems, Wetzlar, Germany) ndi software ya Neurolucida (MicroBrightfield Inc) yokhala ndi ma kamera okonzedwa m'malo onse (pogwiritsa ntchito zolinga za 10x). Pogwiritsa ntchito mapulogalamu a neurolucida, malo ofunika anafotokozedwa molingana ndi zizindikiro (Swanson, 1998) wapadera pa dera lililonse la ubongo (onani Chithunzi 1). Midzi yeniyeni ya kusanthula idagwiritsidwa ntchito mmadera onse kupatula NAC core ndi chipolopolo. Kumalo omaliza, kufotokoza kwa PERK ndi Fos kunali kosagwirizana ndipo kunkawoneka ngati mapangidwe ofanana. Choncho, maziko onse ndi chipolopolo adalongosola mothandizidwa ndi zizindikiro (zowonongeka, zowonongeka, ndi zisumbu za Calleja). Madera a kusanthula sanali osiyana pakati pa magulu oyesera, ndipo anali 1.3 mm2 mu core NAC ndi chipolopolo. Makhalidwe apadera a kusanthula malo otsala anali: 1.6 mm2 mu BLA, 2.5 ndi 2.25 mm2 mu MEApd ndi CeA mofanana, 1.0 mm2 mu MPN, 1.25 mm2 m'maboma a BNST ndi a mPFC, ndi 3.15 mm2 mu VTA. Zigawo ziwiri zinkawerengedwera m'madera onse a ubongo pamtundu uliwonse, ndipo chiwerengero cha maselo osakanizidwa ndi awiri omwe analembedwa kuti PERK ndi Fos komanso peresenti ya maselo a PER omwe amasonyeza chizindikiro cha Fos anawerengedwa. Kwa kuyesera 1, 2, ndi 4, magulu a gulu ankafaniziridwa pogwiritsa ntchito njira ziwiri za ANOVA (zifukwa: kukwatira ndi mankhwala) ndi Fisher's LSD posachedwa kufananitsa pa chiwerengero chofunika cha 0.05. Poyesera 3, magulu a gulu anafaniziridwa pogwiritsa ntchito mayeso osayenerera pa chiwerengero cha 0.05.

Chithunzi 1      

Zithunzi zojambulajambula ndi zithunzi zomwe zikuwonetsera madera a ubongo. Malo owonetseredwa akuwonetsedwa anali okhudzana ndi zizindikiro zosiyana kwambiri ndi gawo la ubongo, sizinali zosiyana pakati pa magulu oyesera, ndipo anali 1.25 mm2 mu mPFC madera (a), 1.3 mm2 mu ...

Images

Zithunzi zojambulajambula Chithunzi 3 anagwiritsidwa ntchito pogwiritsa ntchito CCD kamera (DFC 340FX, Leica) yomwe ili pamakina a michere Leica (DM500B) ndipo adatumizidwa ku Adobe Photoshop 9.0 software (Adobe Systems, San Jose, CA). Zithunzi sizinasinthidwe mwanjira iliyonse kupatula kusintha kwa kuwala.

Chithunzi 3      

Zithunzi zoimira zithunzi za NAc zomwe zimapangidwira Fos (red, a, d, g, j) ndi pERK (zobiriwira, b, e, h, k) zinyama za gulu lililonse loyesera: No Sex + Sal (a, b, c) , Sex + Sal (d, e, f), Palibe kugonana + Meth (g, h, i), ndi Sex + Meth (j, k, l). Mapepala abwino ali ...

ZINTHU

Neural Kugwiritsa Ntchito Limbic Kachitidwe ndi Kugonana ndi Meth Administration

Yesetsani 1: Kufufuza kwa maselo amodzi ndi awiri omwe analembedwa kuti apangidwe ndi Fos ndi mankhwala omwe amachititsa kuti amuna apatsidwe Meth 10 maminiti asanapereke nsembe adawulula Fos yomwe imapangidwira mu MPN, BNSTpm, NAc core ndi shell, BLA, VTA, ndi madera onse a mPFC, mogwirizana ndi maphunziro apitayi omwe akuwonetsera kufotokozera kwa Fos komwe kumaphatikiziridwa mmagulu m'madera awa (Baum ndi Everitt, 1992, Pfaus ndi Heeb, 1997, Veening ndi Coolen, 1998, Hull et al., 1999). Utsogoleri wa maselo 10 maminiti asanayambe kupereka nsembe inachititsa kuti pakhale khungu la NAC ndi chipolopolo, BLA, MeApd, CeA, BNSTpl, ndi madera a mPFC, mofanana ndi kusintha kwa mankhwala omwe amachititsa ena psychostimulants (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

Kuwonjezera apo, njira zitatu za kugwiritsirana ntchito kwa neural zochita ndi khalidwe la chiwerewere ndi Meth zinawonedwa: Choyamba, malo a ubongo amadziwika kumene kugonana ndi mankhwala osokoneza bongo amachititsa kuti anthu asagwiritsidwe ntchito ndi neural populations (Gulu 2). Makamaka, mu CeA, MEApd, BNSTpl, ndi mPFC, kuwonjezeka kwakukulu kwa pERK yopangidwa ndi mankhwala osokoneza bongo (F (1,16) = 7.39-48.8; p = 0.015- <0.001) ndi ma Fos opangira zachiwerewere (F (1,16, 16.53) = 158.83-0.001; p <1,16) adawonedwa. Komabe, m'maderawa panalibe kuwonjezeka kwakukulu kwa ma neuroni omwe amatchedwa amuna omwe amathandizidwa ndi Meth. Chokhacho chinali MEApd, pomwe zotsatira zakusakanikirana kwa manambala am'magulu awiri okhala ndi zilembo zidapezeka (F (9.991) = 0.006; p = XNUMX). Komabe, panalibe zotsatira zenizeni za mankhwala osokoneza bongo ndipo kulembedwa kawiri m'magulu ochiritsidwa a Meth sikunali kwakukulu kwambiri kuposa m'magulu amchere amchere, motero sanayambitsidwe ndi mankhwalawa (Gulu 2). Chachiwiri, madera a ubongo anazindikiritsidwa kumene kusinthika kwa neural kunangowonjezera ndi kukwatira (Gulu 3). Mwapadera, MPN, BNSTpm, ndi VTA zinangowonjezeredwa ndi kugwirizanitsa, ndipo zinali ndi kuwonjezeka kwakukulu kwa Fos (F (1,16) = 14.99-248.99; p ≤ 0.001), koma palibe mchitidwe wopangidwa ndi Meth.

Gulu 2      

Zowonjezera za kufotokozera kwa Fos ndi machitidwe opatsirana pogwiritsa ntchito mauthenga m'madera a ubongo komwe kugonana ndi mankhwala osokoneza bongo amachititsa kuti anthu asagwirizane nawo.
Gulu 3      

Zowonjezera za kufotokozera kwa Fos ndi kufotokozedwa kwa Meth kwa pERK m'madera a ubongo kumene neural activation inangotengedwa ndi kukwatira.

Pamapeto pake, madera a ubongo amapezeka kumene kugonana ndi mankhwala osokoneza bongo amachititsa kuti anthu ambiri azikhala ndi matenda osokoneza bongo (Chithunzi 2 ndi And3) .3). Pachimake cha NAc ndi chipolopolo, BLA, ndi ACA, panali zovuta zonse zakukhalitsa (F (1,16) = 7.87-48.43; p = 0.013- <0.001) ndi mankhwala osokoneza bongo (F (1,16) = 6.39– 52.68; p = 0.022- <0.001), komanso kulumikizana pakati pazinthu ziwirizi (F (1,16) = 5.082-47.27; p = 0.04- <0.001; kulumikizana kwakukulu ku ACA) pamasamba amitundu yonse Ntchito yosakanikirana ndi Fos ndi Meth. Post hoc yowunikira idawonetsa kuti manambala amitundu iwiri yotchedwa ma neuron anali okwera kwambiri mwa amuna ojambulidwa ndi Meth poyerekeza ndi mankhwala osagwiritsidwa ntchito a Meth (p = 0.027- <0.001), kapena amate saline (p = 0.001- <0.001) amuna (Chithunzi 2 ndi And3) .3). Pamene deta imasonyezedwa monga magawo a mankhwala osokoneza bongo, 39.2 ± 5.3% mu core NAC, 39.2 ± 5.8% mu NA shell, 40.9 ± 6.3% mu BLA, ndipo 50.0 ± 5.3% ya ACA neurons anayambitsidwa ndi kuwirirana ndi Meth.

Chithunzi 2      

Ma Fos omwe amachititsa kugonana ndi maonekedwe a PERK mu NAC, BLA, ndi ACA neurons 10 min potsatira ulamuliro wa 4 mg / kg Meth. Kutanthauza nambala ± sem ya Fos (a, d, g, j), pERK (b, e, h, k), ndi awiri (c, f, i, l) maselo olembedwa m'kati mwa NAC (a, ...

Chidziwitso chosayembekezereka chinali chakuti khalidwe la chiwerewere linakhudza pERK. Ngakhale kuti Meth inachititsa kuti anthu asagwiritsidwe ntchito m'magulu onse omwe ali ndi ma Meth, omwe ali m'kati mwa NAC, BLA, ndi ACA, kulemba mankhwalawa kunali kochepa kwambiri poyerekeza ndi amuna omwe anajambulidwa ndi Meth poyerekeza ndi amuna omwe sanagwidwe ndi Meth. (Chithunzi 2b, e, h, k; p = 0.017- <0.001). Kupeza kumeneku kungapitirize kutsimikizira lingaliro lakuti kugonana ndi mankhwala kumagwiritsa ntchito neurons yomweyi, komabe zingakhalenso zisonyezero zosinthira kusinthanitsa ndi mankhwala okhudzana ndi mankhwala kapena kagayidwe kamene kamene kameneko kanasintha mayankho a mitsempha kwa Meth. Kuti afufuze ngati chiwerewere chimayambitsa ndondomeko yosiyana ya mankhwala opangidwa ndi mankhwala, zigawo za NAC, BLA, ndi ACA zinadetsedwa kwa amuna omwe anaperekedwa nsembe nthawi ina (15 min) kutsata njira zothandizira mankhwala (kuyesera 2).

Yesetsani 2: Kufufuza kwa maselo osakwatiwa ndi awiri omwe amavomereza kuti zokhudzana ndi chiwerewere ndizochitika kwa Meth 15 maminiti asanapereke nsembe zinawonjezera kuwonjezeka kwakukulu kwa Fos ndi pERK immunolabeling mu NAC ndi chipolopolo, BLA, ndi ACA. Kuonjezera apo, kufotokozera kwakukulu kwa kufotokozera kwa Fos ndi feteleza zopangidwa ndi Meth kunapezanso mmadera awa (Chithunzi 4; Kusakanikirana: F (1,12) = 15.93-76.62; Episodio 0.002- <0.001; zotsatira za mankhwala: F (1,12) = 14.11-54.41; p = 0.003- <0.001). Chiwerengero cha ma neuroni omwe amadziwika kuti ndi amuna omwe ali ndi ma Meth omwe anali ndi ma meth anali okwera kwambiri poyerekeza ndi omwe sanalandire mankhwala a Meth (p <0.001) kapena amuna amchere amchere (p <0.001). Deta ikafotokozedwa ngati kuchuluka kwa ma neuron omwe amagwiritsa ntchito mankhwala osokoneza bongo, 47.2 ± 5.4% (NAc core), 42.7 ± 7.6% (NAc shell), 36.7 ± 3.7% (BLA), ndi 59.5 ± 5.1% (ACA) ya ma neuron omwe adayambitsidwa mwa kukwatira kunayambitsidwanso ndi Meth. Kuphatikiza apo, chizolowezi chomwa mankhwala osokoneza bongo sichinasiyane pakati pa nyama zomwe sizinakwatirane (Chithunzi 4b, e, h, k), m'malo onse kupatula ACA (p <0.001). Izi zikuwonetsa kuti mchitidwe wogonana umasinthiratu mtundu wakanthawi wodalitsika wa Meth.

Chithunzi 4      

Ma Fos omwe amachititsa kugonana ndi maonekedwe a PERK mu NAC, BLA, ndi ACA neurons 15 min potsatira ulamuliro wa 4 mg / kg Meth. Kutanthauza nambala ± sem ya Fos (a, d, g, j), pERK (b, e, h, k), ndi awiri (c, f, i, l) maselo olembedwa m'kati mwa NAC (a, ...

Neural Activation kutsatira zotsatira za kugonana ndi 1 mg / kg Meth

Pakadali pano zotsatira zimasonyeza kuti khalidwe la kugonana ndi 4 mg / kg Zimayambitsa anthu ambiri omwe ali ndi neuroni m'kati mwa NAC ndi shell, BLA, ndi ACA. To kufufuza zotsatira za mankhwala osokoneza bongo pazomwe izi zikuyambitsa, machitidwe a neural activation adaphunziridwanso pogwiritsa ntchito mlingo wotsika wa Meth. Cholinga cha NAC ndi chipolopolo, BLA, ndi ACA chinafufuzidwa chifukwa choyambitsa kugonana ndi Meth. Inde, khalidwe la chiwerewere ndi kuchitidwa kwa Meth kunawonjezera kuwonjezeka kwakukulu kwa Fos ndi pERK immunolabeling mu NAC pakati ndi zigawo za shell, BLA, komanso neurons mu dera la ACA la mPFC (Chithunzi 5). Chochititsa chidwi, mlingo wa m'munsi wa Meth unayambitsa ziwerengero zofanana za pERK zotchedwa neurons zomwe zimapangidwira ndi 4 mg / kg Meth m'madera anayi a ubongo omwe amawerengedwa. Chofunika kwambiri, chidziwitso cha NAC ndi chipolopolo, BLA, ndi ACA chinawonetsa kuwonjezeka kwakukulu kwa chiwerengero cha maselo awiri olembedwa (Chithunzi 5c, f, i, l) poyerekeza ndi amuna osavomerezeka omwe adalowetsedwa ndi Meth (p = 0.003- <0.001). Deta ikafotokozedwa ngati kuchuluka kwa ma neuron omwe amagwiritsa ntchito mankhwala osokoneza bongo, 21.1 ± 0.9% ndi 20.4 ± 1.8% mu NAc pachimake ndi chipolopolo motsatana, 41.9 ± 3.9% mu BLA, ndi 49.8 ± 0.8% ya ma ACA neurons adayambitsidwa ndi kugonana ndi Meth.

Chithunzi 5      

Ma Fos omwe amachititsa kugonana ndi maonekedwe a PERK mu NAC, BLA, ndi ACA neurons 15 min potsatira ulamuliro wa 1 mg / kg Meth. Kutanthauza nambala ± sem ya Fos (a, d, g, j), pERK (b, e, h, k), ndi awiri (c, f, i, l) maselo olembedwa m'kati mwa NAC (a, ...

Neural Activation potsatira khalidwe la kugonana ndi kulamulira d-Amphetamine

Kuwona ngati zotsatirazi zapamwamba zinali zenizeni za Meth, kuyesa kwina kunayesedwera kuti aphunzire za mating- ndi Amph-induced neural activation. Kufufuza kwa maselo amodzi ndi awiri omwe analembedwa kuti PERK ndi Fos adasonyeze kuti khalidwe la kugonana ndi kuwonetsetsa kwa Amph kunabweretsa kuwonjezeka kwakukulu kwa Fos ndi pERK immunolabeling mu NAC pakati ndi chipolopolo ndi BLA (Chithunzi 6; Kusakanikirana: F (1,15) = 7.38-69.71; p = 0.016- <0.001; zotsatira za mankhwala: F (1,15) = 4.70-46.01; p = 0.047- <0.001). Kuphatikiza apo, kuchuluka kwa ma neuron omwe amadziwika kuti anali amtundu wapamwamba kwambiri poyerekeza ndi ma Amph omwe amathandizidwa (p = 0.009- <0.001), kapena amchere amchere amchere (p = 0.015- <0.001) amuna (Chithunzi 6c, f, i). Pamene deta ikuwonetsedwa ngati magawo a mankhwala osokoneza bongo, 25.7 ± 2.8% ndi 18.0 ± 3.2% mu core NAc ndi shell motsatira, ndipo 31.4 ± 2.0% ya BLA neurons anachititsidwa ndi onse mating ndi Amph. Dera la ACA la mPFC linawonetsera maofesi ambiri a Fos (Chithunzi 6j; F (1,15) = 168.51; p <0.001). Komabe, mosiyana ndi Meth, Amph sizinapangitse kuwonjezeka kwakukulu kwa kuchuluka kwa mankhwala osokoneza bongo mu ACA (Chithunzi 6k) kapena manambala a awiri omwe amatchedwa neurons mu ACA (Chithunzi 6l) poyerekeza ndi amuna onse omwe ali ndi jekeseni ndi amchere omwe sagwidwa.

Chithunzi 6      

Mafilimu opatsirana pogonana omwe amachititsa kugonana ndi amphitikiti m'kati mwa NAc, BLA, ndi ACA neurons 15 min potsatira ulamuliro wa 5 mg / kg Amph. Kutanthauza nambala ± sem ya Fos (a, d, g, j), pERK (b, e, h, k), ndi awiri (c, f, i, l) maselo olembedwa m'kati mwa NAC (a, ...

KUKANGANANI

Kafukufuku wamakono akuwonetsera pamtunda wamagetsi kugwirizanitsa pakati pa neural activation ndi khalidwe lachilengedwe lolimbikitsa kugonana ndi psychostimulant Meth. Choncho, ma datawa amasonyeza kuti mankhwala osokoneza bongo amachititsa kuti madera omwewo awononge mphotho, koma kwenikweni, mankhwalawa amachititsa kuti maselo omwewo agwiritsidwe ntchito poyendetsera mphotho. Mwachindunji, zinasonyezedwa apa kuti khalidwe la kugonana ndi Meth linagwirizanitsa chiwerengero cha neurons mu NAC core ndi shell, BLA, ndi ACA dera la mPFC, kudziwitsa malo omwe Ameth angakhudze khalidwe la kugonana.

Zomwe zikuchitika panopa kuti khalidwe la chiwerewere ndi kulamulira kwa Meth kuyambitsa mitundu yambiri ya ziphuphu za NAC, BLA, ndi ACA zimasiyana ndi zofukufuku zofukufuku zomwe zikusonyeza kuti anthu osiyanasiyana a NAC amatha kupeza mphoto ndi mankhwala.

Mwapadera, maphunziro a electrophysiological omwe amafanizira machitidwe a neural pamene akudzilamulira okha madalitso (mwachilengedwe ndi chakudya) ndi intravenous cocaine awonetsa kuti cocaine kudziyendetsa bwino inachititsa kuti kusiyana, kuphatikizapo anthu osakanikirana a neuroni omwe kawirikawiri sikumvetsera panthawi yogwira ntchito madzi ndi kulimbikitsa chakudya (92%). 8% yokha ya mavotolo owonetsa amachititsa kuti ayambe kugwira ntchito ndi cocaine ndi mphotho yachilengedwe (Carelli et al., 2000).

Mosiyana ndi zimenezi, ambiri (65%) a selo mu NAC adasonyeza kuyanjana ndi mphoto zosiyana siyana (chakudya ndi madzi), ngakhale ngati wina alimbikitsa (sucrose) (Roop et al., 2002).

Zowonjezera zifukwa zingapo zakhala zikuthandizira kusokonezeka ndi zotsatira zamakono. Choyamba, njira zosiyana zamagwiritsidwe ntchito zinkagwiritsidwa ntchito kufufuza ntchito za neural. Kafukufuku wamakono adagwiritsa ntchito njira yodziwiritsira ntchito njira zachinsinsi zodziwiritsira ntchito njira zowonongeka za neural ndi njira ziwiri zosiyana siyana pogwiritsira ntchito timadzi timene timatulutsa timadzi timene timayambitsa matenda a Fos ndi pERK. Mosiyana ndi zimenezi, maphunziro a Carelli ndi ogwira nawo ntchito amagwiritsa ntchito ma electrophysiological zolembedwera ku NAC ya zinyama zokhazokha kuti zithetse ngati mankhwala omwe amachitira nkhanza amachititsa kuti dera loperewera likhale lofanana.

Chachiwiri, kafukufuku wamakono akufufuzira mphotho yosiyana ya chilengedwe monga khalidwe logonana poyerekeza ndi maphunziro apitalo, omwe amagwiritsira ntchito chakudya ndi madzi mu makoswe oletsedwa (Carelli, 2000). Chakudya ndi madzi zingakhale zopindulitsa pang'ono kusiyana ndi kukwatira. Mchitidwe wogonana ndi wopindulitsa kwambiri ndipo makoswe amapanga mosavuta CPP kuti agwirizane (Agmo ndi Berenfeld, 1990, Martinez ndi Paredes, 2001, Tenk, 2008). Ngakhale, makoswe oletsa zakudya amapanga CPP kwa madzi (Agmo et al., 1993, Mafuta ndi Clifton, 1997) ndi chakudya (Mafuta ndi Clifton, 1997), dMitsuko yosasinthika bwino imadya ndi kupanga CPP kwa zakudya zowonjezera (Jarosz et al., 2006, Jarosz et al., 2007).

Chachitatu, maphunziro athu anaphatikizapo mankhwala osiyanasiyana ozunzidwa poyerekeza ndi maphunziro apitalo, pogwiritsa ntchito methamphetamine ndi amphetamine mmalo mwa cocaine. Zotsatira zamakono zikuwonetsa kuti Meth makamaka, ndi amphetamine mochepetsetsa, zinayambitsa kuchitidwa kwa neuroni kumayendetsedwa ndi khalidwe la kugonana. Chidziwitso cha mankhwala osokoneza bongo chiyenera kuti chinathandizanso pa zomwe tapeza. Kafukufuku wamakono adagwiritsa ntchito zinyama zomwe anali nazo zogonana, koma ndiïve mankhwala. Mosiyana ndi zimenezi, maphunziro a Electrophysiological a Carelli ndi ogwira nawo ntchito amagwiritsidwa ntchito "nyama zophunzitsidwa bwino" zomwe zimapezeka mobwerezabwereza ku cocaine.

Choncho, n'zotheka kuti kuyambitsidwa kwa Meth kokhala ndi neuroni yochitidwa ndi khalidwe la chiwerewere kumasinthidwa ndi makoswe odziwa mankhwala. Komabe, maphunziro oyambirira kuchokera ku lab athu amati chidziwitso cha mankhwala sichitha kukhala chinthu chachikulu monga khalidwe la chiwerewere ndi mankhwala amtundu mwa amuna omwe amachitidwa mosavuta ndi Meth ogwirizanitsa nawo ofanana ndi mankhwala omwe amachititsidwa ndi mankhwalawa (20.3 ± 2.5% mu NAC core ndi 27.8 ± 1.3% mu NAc shell; Frohmader ndi Coolen, zolemba zosasindikizidwa).

Pomalizira, kafukufuku wamakono akufufuzira njira "yowongoka" ya mankhwala osokoneza bongo akugwiritsa ntchito kayendetsedwe kowonongeka. Choncho, kusanthula komweku sikukuwunikira mauthenga othandizira maulendo a neural omwe akuphatikizapo mankhwala osokoneza bongo kapena mankhwala omwe amagwiritsidwa ntchito ndi mankhwala, komabe amavumbulutsa ntchito zachisokonezo zomwe zimayambitsa mankhwala osokoneza bongo. M'maphunziro a kale omwe asayansi amagwiritsa ntchito, NAc neural zochitika zomwe zimachitika mumasekondi ochepa a mayankho osamaliridwa sizotsatira zotsatira za mankhwala a cocaine, koma zimadalira kwambiri zinthu zomwe zimagwirizana ndizokhazikitso (paradigm)Carelli, 2000, Carelli, 2002). Mwachindunji, NAc neural activity ikukhudzidwa ndi machitidwe odziimira okha omwe amachititsa chidwi ndi mankhwala omwe amagwiritsidwa ntchito ndi intravenous cocaine komanso njira zothandizira (ie, kuthamanga kwa chiwindi)Carelli, 2000, Carelli ndi Ijames, 2001, Carelli, 2002, Carelli ndi Wightman, 2004). Mwachifupikitso, zomwe tinazipeza pakugwirizanitsa ndi mphotho ndi zakumwa za mankhwala zingakhale zenizeni zowonongeka ndi khalidwe la chiwerewere ndi kuperekedwa mosavuta Meth ndi Amph.

Meth ndi kugonana zimasokoneza anthu ambiri omwe amapezeka m'matumbo a NAC ndi chipolopolo pogwiritsira ntchito mlingo. Nkhono zomwe zimagwiritsidwa ntchito pamodzi mu NAC zingathe kukambirana zotsatira za Meth pazimene zimakhudzanso khalidwe la kugonana monga zilonda za NAC zimasokoneza chiwerewere (Liu et al., 1998, Kippin et al., 2004). Kuwonjezera pamenepo, ma neuroniwa akhoza kukhala locus chifukwa cha mankhwala okhudzana ndi mankhwala okhudzana ndi kumwa mankhwala, chifukwa mitsempha ya m'munsi yochepa (1 mg / kg) inachepetsa chiwerengero cha maselo awiri olembedwa ndi 50% poyerekeza ndi mlingo wapamwamba wa Meth (4 mg / kg). Ngakhale kuti phunziroli silikudziwika ndi mankhwala otchedwa phenypetic, afukufuku wapitawo asonyeza kuti pERK ndi Fos mafotokozedwe opangidwa mu mankhwalawa ndi NAC zimadalira onse a dopamine (DA) ndi a thoutamate receptors (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). Ngakhale sizikudziwikiratu ngati kugwiritsidwa ntchito kosokoneza ubongo ku NAC kumadalira zowonjezera, izi zawonetsedwa m'madera ena a ubongo,Lumley ndi Hull, 1999, Dominguez et al., 2007). THus, Meth angagwiritse ntchito ma neuroni atayambitsanso panthawi yogonana pogwiritsa ntchito dopamine ndi receptors za glutamate. Udindo wa NAc wokhudzana ndi chiwerewere sichikudziwikiratu, koma zakhazikitsidwa bwino kuti DA imakhala ndi zofunikira kwambiri pa chilakolako cha kugonana (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). Maphunziro a Microdialysis adanena kuti kuwonjezeka kwa NAc DA efflux panthawi yovuta komanso yothetsera kugonana kwa amuna (Fiorino ndi Phillips, 1999a, Lorrain et al., 1999) ndipo masolimbic DA efflux yalinganizana ndi kuwonetsera koyambitsa ndi kukonza khalidwe la kugonana kwa makoswe (Pfaus ndi Everitt, 1995). Kuwonjezera apo, maphunziro a DA opanga ziwonetsero akusonyeza kuti DA otsutsana nawo mu NAC amaletsa khalidwe la kugonana, pamene agonist amachititsa chizolowezi chogonanar (Everitt et al., 1989, Pfaus ndi Phillips, 1989). Motero, Meth ingawononge chilakolako cha khalidwe la kugonana pogwiritsa ntchito mapulogalamu a DA.

Mosiyana ndi NAC, chiwerengero cha maselo awiri omwe analembedwa mu BLA ndi ACA sanasinthe mosasamala kanthu za mlingo wa Meth. BLA ndi yofunika kwambiri pa maphunziro osamvetsetseka komanso amagwira ntchito mwakhama ndikupindula pothandizira (Everitt et al., 1999, Cardinal ndi al., 2002, Onani, 2002). BLA anawonetsa makoswe akuwonetsa kuchepa kwa chiwindi kutsogolo kwa zovuta zomwe zimaphatikizana ndi chakudya (Everitt et al., 1989) kapena kugwirizanitsa kugonana (Everitt et al., 1989, Everitt, 1990). Mosiyana ndi izi, kusokoneza kumeneku sikumakhudza gawo la kudya ndi khalidwe lachiwerewere (Cardinal ndi al., 2002). BLA imathandizanso kuti zikumbukire zokhudzana ndi mankhwala osokoneza bongo (Grace ndi Rosenkranz, 2002, Laviolette ndi Grace, 2006). Zilonda kapena mankhwala osokoneza bongo a BLA amaletsa kugula (Whitelaw et al., 1996) ndi mawu (Grimm ndi See, 2000) kubwezeretsedwa kophika kocaine, komabe sikumakhudza njira yogwiritsira ntchito mankhwala osokoneza bongo. Komanso, Amph analowetsa mwachindunji ku BLA zotsatira mu kubwezeretsedwa kwa mankhwala osokoneza bongo pamaso pa zidazo (Onani ndi al., 2003). Choncho, n'zotheka kuti kupititsa patsogolo kwa psychostimulant kwa DA ku BLA kumabweretsa mavuto osokoneza maganizo komanso kufunafuna (Ledford et al., 2003) zokhudzana ndi kugonana, motero kumathandizira kugwirizanitsa kugonana ndi chikhumbo chokhudzidwa ndi ozunza a Meth (Semple et al., 2002, Green ndi Halkitis, 2006).

Ku ACA, neural activation ya kugonana activated neurons anali mlingo-wodziimira ndi enieni kwa Meth, monga sizinasinthike ndi Amph. Ngakhale Meth ndi Amph ali ndi zikhalidwe zofanana ndi zamagetsi, Meth ndi psychostimulant yochuluka kwambiri kuposa Amph ndi yotalikirapo (NIDA, 2006). Maphunziro a Goodwin et al. Anasonyeza kuti Meth imapanga DA yochuluka kwambiri ndipo imalepheretseratu kuti DA imagwiritsidwa ntchito m'deralo mokwanira kwambiri mu khola la NAc kuposa Amph. Makhalidwe amenewa angapangitse kuti Meth ayambe kumwa mankhwala osokoneza bongo poyerekeza ndi Amph (Goodwin et al., 2009) ndipo mwina kusiyana kwa ma neural pakati pa mankhwala awiriwa. Komabe, sizikuwonekeratu ngati zosiyana za zotsatira zimachokera ku kusiyana kwa mphamvu pakati pa mankhwala kapena mankhwala okhudzana ndi mankhwala omwe akugwiritsidwa ntchito komanso kufufuza kofufuzira n'kofunika.

Kugwirizanitsa ndi Meth ndi kugonana sikunali kuchitika m'madera ena a mPFC (IL ndi PL). Mu khola, ACA yakhala ikuphunzira mozama pogwiritsa ntchito ntchito zokhutiritsa, zothandizira gawo mu mayanjano a stimulus-reinforcer (Everitt et al., 1999, Onani, 2002, Cardinal ndi al., 2003). Pali umboni wochuluka wosonyeza kuti mPFC ikukhudzidwa ndi chilakolako cha mankhwala ndi kuyambiranso kugwiritsira ntchito mankhwala osokoneza bongo komanso mankhwala osokoneza bongo. (Grant et al., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin ndi See, 2003, Shaham et al., 2003, Kalivas ndi Volkow, 2005). IneZogwirizana ndi izi, zafotokozedwa kuti kupweteka kwa mPFC chifukwa cha kubwerezabwereza kwa mankhwala osokoneza bongo kungakhale koyambitsa kuchepetsa kugwiritsira ntchito mankhwala osokoneza bongo komanso kuwonjezeka kwa khalidwe la mankhwala osokoneza bongo monga momwe amachitira anthu ambiri oledzera (Jentsch ndi Taylor, 1999). Deta yaposachedwa kuchokera ku labotore yathu inasonyeza kuti mPFC zilonda zimayambitsa kupitiriza kufunafuna khalidwe la kugonana pamene izi zinkakhudzidwa ndi kutengeka kwakukulu (Davis et al., 2003). Ngakhale kuti phunziroli silinayambe kufufuza za ACA, limagwirizana ndi lingaliro lakuti mPFC (ndi ACA makamaka) imayanjanitsa zotsatira za Meth chifukwa cha kusowa kwa chiletso choletsa chiwerewere monga momwe amanenera ndi azimayi a Meth (Salo et al., 2007).

Pomalizira, palimodzi maphunzirowa amapanga njira yofunikira yoyamba kumvetsetsa bwino momwe kumwa mowa mwauchidakwa kumayendera njira za neural zomwe nthawi zambiri zimayanjanitsa mphotho zachilengedwe. Komanso, zotsatirazi zikusonyeza kuti mosiyana ndi chikhulupiliro chaposachedwapa chakuti mankhwala osokoneza bongo satsegula maselo omwewo m'masolambic monga mphotho yachilengedwe, Meth, ndi Amph, kuchepetsa maselo omwewo monga khalidwe la chiwerewere. Komanso, izi zothandizidwa ndi neural populations zingakhudze kufunafuna mphotho zachilengedwe pambuyo poyera mankhwala. Potsirizira pake, zotsatira za phunziroli zingathandize kwambiri kuti timvetsetse za chizolowezi choledzera. Kuyerekeza kwa kufanana ndi kusiyana kwake, komanso kusintha kwa neural activation ya masolimbic dongosolo opangidwa ndi chiwerewere motsutsana ndi mankhwala osokoneza bongo kungachititse kumvetsa bwino kugwiritsa ntchito mankhwala osokoneza bongo ndi kusintha komwe kumagwirizana ndi mphotho zachilengedwe.

Kuvomereza

Kafukufukuyu anathandizidwa ndi mabungwe ochokera ku National Institutes of Health R01 DA014591 ndi ku Canada Institutes of Health Research RN 014705 ku LMC.

ZIZINDIKIRO

  • ABC
  • avidin-biotin-horseradish peroxidase yovuta
  • ACA
  • anterior cingulate malo
  • Amph
  • d-amphetamine
  • BLA
  • basolateral amygdala
  • BNSTpl
  • Pachiyambi pogona la stria terminalis
  • BNSTpm
  • Chiyambi cha bedi la stria terminalis
  • BT
  • biotinylated tyramide
  • CeA
  • cental amygdala
  • CPP
  • malo okonda malo
  • E
  • kuthamangitsidwa
  • EL
  • kuthamanga kwa latency
  • IF
  • malo a infralimbic
  • IL
  • kupititsa patsogolo
  • IM
  • kusokoneza
  • M
  • Phiri
  • MAP Kinase
  • mapuloteni kinase opangidwa ndi mitogen
  • PAMENE
  • amygdala apakati
  • Meth
  • methamphetamine
  • ML
  • phiri latency
  • mPFC
  • mphalapala yamkati
  • MPN
  • chithunzithunzi chamkati chamkati
  • NAc
  • nucleus Accumbens
  • PB
  • phosphate buffer
  • PBS
  • Phosphate yodulidwa mchere
  • PEI
  • posachedwa nthawi yopuma
  • PERK
  • MAP Kinase
  • PL
  • malo oyambirira
  • VTA
  • malo amtunda

Mawu a M'munsi

Chodzikanira cha Wosindikiza: Imeneyi ndi fayilo ya PDF ya zolembedwa zosavomerezeka zomwe zavomerezedwa kuti zifalitsidwe. Monga ntchito kwa makasitomala athu ife tikupereka malemba oyambirira a zolembedwazo. Mipukutuyi idzayambanso kujambula, kufotokozera, ndi kubwereza umboni umene umapezekapo musanatulutsidwe mawonekedwe ake omalizira. Chonde dziwani kuti panthawi yopanga zolakwika zingapezeke zomwe zingakhudze zomwe zili, komanso zotsutsana ndi malamulo zomwe zimagwiritsidwa ntchito pa magaziniyo.

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