Izinguquko ezinamandla ku-Nucleus Accumbens Dopamine Efflux Ngesikhathi se-Coolidge Impumelelo kuma-Rats wama-Male (i-1997)

I-YBOP COMMENTS: Umphumela we-Coolidge ungemuva kwamandla we-Internet porn. Umphumela we-Coolidge yinto ebonakalayo ezinhlotsheni zezilwane ezincelisayo lapho abesilisa (kanye nabesifazane abambalwa) bekhombisa intshisekelo yokuvuselela ubulili uma bethulwa abalingani abasha abathandanayo abathandanayo, noma sebenqabile ucansi kusuka ngaphambili kepha isekhona abalingani abathandana nabo kwezocansi. Amanoveli okuya ocansini agcwele le ndawo ngentsha evuselelwe ebangelwa yi-dopamine ephezulu. Ukusakazwa okuqhubekayo kwezinto ezintsha yikho okwenza i-inthanethi ye-porn ihluke kangaka ku-porn yesikhathi esedlule.

Isihloko sokuqala, ngamagrafu

  1. UDennis F. Fiorino,
  2. I-Ariane Coury, futhi
  3. U-Anthony G. Phillips

+Bonisa ukusebenzisana

  1. I-Journal of Neuroscience, 15 Juni 1997, 17 (12): 4849-4855;

abstract

Umphumela we-Coolidge uchaza ukuvuselelwa kokuziphatha ngokobulili "isilwane" esisondelene ngocansi ngokuphendula kumlingani omamukelayo weveli. Njengoba inikezwe indima ye-mesolimbic dopamine (i-DA) ohlelweni lokuqaliswa nokugcinwa kokuziphatha okugqugquzelayo, i-microdialysis yasetshenziselwa ukuqapha ukudluliswa kwe-nucleus accumbens (NAC) ngesikhathi sokubambisana, ukuhlukunyezwa ngokocansi nokuvuselelwa kokuziphatha ngokocansi. Ngokuvumelanisa nemibiko yangaphambilini, isethulo se-estrous wesifazane ngemuva kwesikrini nokuhlanganiswa kwakuhlobene nokunyuka okuphawulekayo ku-NAC DA efflux. Ukubuya kwezinguquko ze-NAC DA kuya kumagugu okuqala okuhambisana nesikhathi sokuhlukunyezwa ngokocansi, nakuba ukuxilongwa kwe-metabolites ye-DA, i-dihydroxyphenylacetic acid ne-homovanillic acid, yahlala iphakanyisiwe. Isethulo sezinsikazi ezamukelayo ngemuva kwesikrini senze ukwanda kancane kwe-DA ye-NAC, eyathuthukiswa ngokuphawulekayo ngesikhathi sokuvuselelana okusha ne-female female. Idatha yamanje ibonisa ukuthi izakhiwo zokuvuselela zowesifazane omusha we-novel zingase zenze ukwandisa ukuhanjiswa kwe-NAC DA kumlingani wesilisa ohlukunyezwa ngokocansi, futhi lokhu kungase kuhlobene nokuvuselelwa kokuziphatha ngokocansi.

Isingeniso

Isilwane esingamaduna esiye sabonisana nesifo satiety singasuswa ukuba siphinde sishade uma owesifazane wokuqala efakwe esikhundleni sensikazi eyamukelekayo. Lokhu sekuyaziwa njengomphumela weCoolidge futhi kubonwe ezinhlobonhlobo zezinhlobo zama-mammalian (U-Wilson et al., I-1963). Izinto ezinjengokukhathala noma ukucindezeleka kwamamoto azanele ukuchaza isimo esicacile sokusondelana ngokobulili, ngoba isenzo esisuka kumuntu wezinsikazi singakwazi ukudala ukuhlangana. Ukuhlukumezeka ngokocansi kungabuye "kuguqulwe" ngokwemithi, ngokwezinga elibalulekile, ngokuphathwa kwezidakamizwa ezihlukahlukene ezingahle zenze izinhlelo ezahlukene ze-neurotransmitter. Lezi zidakamizwa zifaka i-yohimbine, i-8-OH-DPAT (U-Rodriguez-Manzo noFernandez-Guasti, i-1994, 1995a), i-nalaxone (I-Pfaus ne-Gorzalka, i- 1987; U-Rodriguez-Manzo noFernandez-Guasti, i-1995a,b), ne-apomorphine (Mas et al., 1995c). Nakuba isenzo sezinto eziphathelene nalezi zidakamizwa asikwazi ukukhishwa (isibonelo, imiphumela ye-adrenergic emisebenzini ye-erectile), imiphumela emiphakathini esemaphakathi ehambisana nokuhlukunyezwa ngokocansi iye yahlongozwa ngesisekelo sokuhlola okuphakathi kwe-noradrenergic lesion (U-Rodriguez-Manzo noFernandez-Guasti, i-1995a) kanye nezivivinyo ze-microdialysis ezihlolisise i-dopaminergic metabolism endaweni yangaphambili yangaphambili (Mas et al., 1995a,b).

Njengoba kunikezwe ukuthi izindlela eziphambili zingase zihambisane nokuvuselelwa kwesimo sokuziphatha ngokobulili isimo somphumela weCoolidge, umuntu obhekene naso yi-eyelimbic dopamine (DA) uhlelo, oluvela endaweni ye-ventral eya eNAC. I-DA ye-Mesolimbic ibonakala isebenza njengesimoduli esiyisisekelo ezinkambisweni zokuhlanganiswa eziyinkimbinkimbi ezibandakanya ukuhlolwa kwezindlela ezithinta imvelo, njengezici ezivela kumuntu olalelayo ngokocansi, kanye nokuhlelwa kwemikhuba eqondiswa imigomo, kubandakanya ukuhlangana (Fibiger noPhillips, i-1986; I-Blackburn et al., I-1992; Phillips et al., 1992; LeMoal, i-1995; Salamone, 1996).

Nakuba i-midbrain i-DA ne-neurons isabela kumvuzo oyinhloko kanye nokukhomba ukubikezela komvuzo, inoveli noma ukungazibikezeli kwemvelo yesikhuthazo kwenza ukuthi i-neuronal isebenze ngokuqinile ngokuphindaphindiwe ngezikhathi zokuqeqeshwa eziphindaphindiwe (I-Fabre et al., I-1983; I-Schultz, i-1992; Mirenowicz no-Schultz, i-1994). Kunobufakazi obuningi obusekela indima ebalulekile yokugqugquzela i-mesolimbic DA ekuqalisweni nasekugcinweni kokuziphatha ngokocansi (rat)U-Pfaus no-Everitt, i-1995), futhi umbiko wezibalo ezincane we-microdialysis ukwandisa ku-NAC DA efflux ngesikhathi sokuphazamiseka nokuqhathaniswa kokuziphatha ngokobulili wesilisa (I-Pfaus et al., I-1990; Pleim et al., 1990; Damsma et al., 1992; I-Wenkstern et al., I-1993; I-Fumero et al., I-1994; Mas et al., 1995b). Kodwa-ke, kukhona idatha encane kakhulu mayelana ne-syringal neurochemical of satiation ngokocansi kanye nokuvuselelwa kokuziphatha ngokobulili. Ukusetshenziswa kwe vivo i-microdialysis ukuqapha i-nelitransmission ye-DA ye-mesolimbic ngesikhathi somphumela we-Coolidge inikeza ithuba eliyingqayizivele lokuhlola indima ye-DA ye-NAC ekuhlanganyeleni, ukuxhaswa ngokocansi nokuvuselelwa kokubambisana.

Ukuhlolwa kwe-microdialysis kwenziwa ukuze kunqume lokhu okulandelayo: (1) ukuthi ukuqala kokuzibandakanya ngokobulili kuhambisane nokubuyiswa kwezingxenyana ze-DA ezingaphezulu kwe-NAC kumanani wokubala noma ngezansi, futhi (i-2) noma ukubuyiselwa kokuziphatha okukopisayo " ukuhlukunyezwa ngokocansi "isilwane esilisa nendoda esamukelekayo yenombolo ihambisana nokunyuka kwe-NAC DA efflux.

IZIMPAHLA NEZINDLELA

Izihloko. Amagundane amaSprague Dawley, atholakala kwi-Animal Care Centre (eYunivesithi yaseBrithani Columbia), namagundane ase Long-Evans, atholakala kuCharles River Canada (eSt. Constant, eQuebec, Canada), ayehlala emagcekeni omcingo (18) × 25 × 65 cm; amakamelo amahlanu ngamakamelo ahlukene e-colony. Amakamelo e-Colony agcinwe ekushiseni kwe ~ ~20 ° C embukisweni we-12 hr ukukhanya / umnyama obuseduze. Amagundane abe nokufinyelela okungenamkhawulo kokudla (iPurina Rat Chow) namanzi.

Ukuhlinzwa nokuhlolwa kokuziphatha ngaphambi kwe-microdialysis yobuchopho.Amagundane amantombazane ayengama-ovariectomized bilaterally ngaphansi kwe-halothane gas anesthesia (Fluothane, Ayerst Laboratories) okungenani amasonto e-4 ngaphambi kokuvivinywa. Ukwamukelwa ngokocansi kuma-stimulus abesifazane kubangelwa izijovo ezingaphansi kwe-estradiol benzoate (i-10 μg) ne-progesterone (i-500 μg), i-48 ne-4 hr, ngokulandelana, ngaphambi kweseshini ngasinye sokuhlola. Amagundane abesilisa ahlolwe ukuziphatha ngokocansi ngezikhathi ezimbili, ukuhlukaniswa kwe-4, ezindaweni zangaphansi kwe-Plexiglas (35 × 35 × 40 cm) ngezingcingo zomhlabathi. Ama-rats abesilisa kuphela afinyelele ku-criterion yokusebenza, okubandakanya ukungena ngaphakathi kwe-5 min ye-presentation ye-female kanye nokujula ngaphakathi kwe-15 min kokungenwa kokuqala, ngesikhathi kuvivinywa ukuhlolwa kokubili ukufakwa kwe-microdialysis probe guide cannulae.

Amagundane (n = I-5) yayisetshenzisiwe nge-ketamine hydrochloride (i-100 mg / kg, i-ip) ne-xylazine (i-10 mg / kg, i-ip) ngaphambi kokuhlinzwa kwe-stereotaxic. I-microdialysis probe guide cannulae (i-19 gauge) yasungulwa ngokuphindaphindiwe phezu kwe-NAC (izixhumanisi ezivela ku-bregma: kwangaphakathi, + 1.7 mm; emaphakathi, ± 1.1 mm; i-ventral, -1.0 mm; i-skull flat) futhi yaxhunywa ku-skull ngama-acrylic yamazinyo futhi izikhonkwane ze-jeweler's. Izimpande zomhlahlandlela we-canonulae ezibhekiswe emzimbeni zasetshenziselwa ukukhulisa ithuba lokuhlola okuphumelelayo kwe-microdialysis. Ngenhlanhla, kulesi silingo samanje, kwakungadingeka kuphela ukukhansela okwenziwe kumlingisi ngamunye. Amagundane angamadoda ayehlelwe ngamabhodlela amakhulu epulasitiki ngamabhodlela amakhulu okudla okunye okusele. Ngemva kwesonto ngemuva kokuhlinzwa, amagundane ahlolwe ukuziphatha ngokocansi. Ngalesi sigaba sokuqeqeshwa, ikamelo lokuhlola lalihlome isikrini se-Plexiglas esilahla ikamelo ekamelweni elikhulu nezincane. Amagundane abesilisa angena ekamelweni elikhulu kanye ne-15 min kamuva, owesifazane wabekwa ngemuva kwesikrini. Ngemuva kwesikhathi sokulungiselela okwesikhashana se-15, isikrini susiwe, futhi amagundane avunyelwe ukulinganisa i-30 min. Izikhathi ezintathu zokuqeqesha zaqhutshwa, eyodwa yi-4 d. Wonke amagundane afinyelele umgomo wokusebenza ngesikhathi ngasinye.

Ukuhlolwa komphumela we-Coolidge. Amagundane ahlanganiswe nge-unilaterally nge-microdialysis probes i-12-18 hr ngaphambi kokuhlolwa komthelela we-Coolidge futhi afakwa egumbini elikhulu legumbi lokuhlola ngokufinyelela mahhala kokudla namanzi. Ngakusasa kokulinga, amasampuli e-microdialysis aqoqwe njalo kumaminithi we-15. Ukuhlolwa kwakunezigaba ezilandelayo eziyisikhombisa ezilandelanayo: (1) isisekelo (okungenani i-60 min); (2) wesifazane i-1 ngemuva kwesikrini (i-15 min); (3) ukukopiselana ne-female 1 kuze kube yisikhathi samaminithi angu-30 esingadluli; (4) ukubuyiswa kabusha kwe-female 1 ngemuva kwesikrini (i-15 min); (5) ukufinyelela ku-1 wesifazane isikhathi se-15 uma kungenakho ukuphakama (uma ukukhuphuka kwenzeka, lesi sigaba sasiphathwa njengesigaba 3); (6) isingeniso se-female 2 ngemuva kwesikrini (i-15 min); 7) ukukopisana ne-female 2 ye-60 min.

Ukuziphatha kwenzelwe ukukhanya okuphansi usebenzisa uhlelo lwevidiyo ye-JVC futhi kugcinwe kwi-video yokuqapha engaphandle kwekamelo lokuhlola. Izindlela ezijwayelekile zokuziphatha ngokobulili zarekhodwa usebenzisa ikhompyutha kanye nesofthiwe efanele (Holmes et al., 1987).

Ngemva kokuhlolwa kwe-microdialysis, izilwane zanikezwa ngokweqile kwamanzi e-chloral futhi zangcoliswa ngokungahambi kahle nge-saline ne-formalin (i-4%). Ama-Brain ahlanjululwa futhi aqhwaqwe, futhi, ngemva kwalokho, izigaba ze-coronal zazihlanjululwe nge-cresyl violet ukunquma ukubekwa kwe-prodidiysis probes. Ama-rats kuphela anezinhlelo zokufaka ama-probe ngaphakathi kwe-NAC asetshenziselwa ukuhlaziywa kokuziphatha neyeurochemical.

I-Microdialysis ne-HPLC-electrochemical detection. I-microdialysis probes yayigxile ekuklanyeni nge-membrane engenazimpande ezingenakubalwa (i-2 mm membrane evuliwe, i-340 μm ububanzi obungaphandle, i-65000 isisindo somzimba we-cutoff, i-Filtral 12, i-Hospal) ekupheleni kwe-distal. Ama-probe asetshenziswe ku-1.0 μl / min ngesisombululo se-Ringer's modified (0.01 m sodium phosphate buffer, pH 7.4, 1.3 mmCaCl2, 3.0 mm KCl, 1.0 mmMgCl2, I-147 mm NaCl) usebenzisa isirinji esisiwe (Hamilton, Reno, NV) kanye nepompo ye-syringe (imodeli 22, Harvard Apparatus, South Natick, MA). Ikholomu yomhlahlandlela we-microdialysis ipolishi yasetshenziselwa ukuvikela iphreyidi ye-microdialysis ngaphakathi kwe-cannon. Ikhoyili yensimbi, enamathele emzimbeni wamanzi (Instech 375s) aphakanyiswe phezulu ekamelweni lokuhlola, isetshenziselwa ukuvikela isithwebuli se-probe (Fiorino et al., 1993).

I-microdialysate i-analytes, eyayihlanganisa i-DA nama-metabolites ayo i-dihyroxyphenylacetic acid (i-DOPAC) ne-homovanillic acid (HVA), yahlukaniswa i-chromatography yesigaba esilandelayo (i-Ultrasphere ikholomu; i-Beckman, i-Fullerton, i-CA, i-ODS 5 μm, i-15 cm, i-4.6 mm, ububanzi obungaphakathi ) usebenzisa i-0.083m i-acetate buffer, pH 3.5 (5% methanol). Ukucubungula kwe-Analyte kwakucatshangwa yi-electrochemical (EC). I-apparatus yayinepompo ye-Bio-Rad (Richmond, CA), i-Valco Instruments (i-Houston, TX) i-EC10W injector-position, i-ESA (Bedford, MA) i-Coulochem II EC nomtshina we-EC kanye nomrekhodi weshadi lomzila wesiteshi (i-Kipp kanye neZonen, iBohemia, NY). Imikhawulo ye-electrochemical detector yilokhu okulandelayo: i-electrode 1, + 450 mV; i-electrode 2, -300 mV; futhi ulinde iseli, -450 mV. Amaprosesa asetshenziselwa ukuhlolwa kabusha, aqhutshwa kwesibeletho futhi ekamelweni lokushisa, kwakuyi-22% yeDA, i-18% ye-DOPAC, ne-18% ye-HVA.

IZIPHUMA

Ukuziphatha

Izinyathelo zokuziphatha kusukela ekuhloleni komphumela we-Coolidge zinikezwe kuThebula 1. I-latency yokumisa, i-intromit, ne-ejaculate, kanye nekhefu lokuthutha ngemuva kokuphuma kokuqala kufana nalabo eseshini yokuqeqesha yangaphambilini (idatha engaboniswa). Lokhu kusikisela ukuthi inqubo ye-microdialysis ayizange iguqule ukuziphatha okuvamile ngokobulili. Ukuthuthukiswa kokuxilongwa ngokocansi, njengoba kuboniswe inombolo ejaculations ngaphambi kokuba kuhlangatshezwe umgomo (7.8 ± 0.5), ukwehla okuqhubekayo kwinani le-intromissions elingaphambi kokukhipha, kanye nokunyuka okuqhubekayo kwesikhashana sokuthutha (idatha engaboniswa) , yayifana nalokhu okubikiwe ezifundweni zangaphambilini (Ibhishi neJordani, i-1956; I-Fowler no-Whalen, i-1961; Fisher, 1962; I-Bermant et al., 1966; U-Rodriguez-Manzo noFernandez-Guasti, i-1994; Mas et al., 1995d). Ukuhlukahluka komuntu ngamunye kwaqashelwa ngokuqondene nenani le-ejaculations elizuzwe ne-female 1, isikhathi esichithwa ukuxubana ne-female 1, nenani lezethulo ze-1 yabesifazane elidingekayo ukuze kufinyelele umbandela we-satiation (ithebula 1, ngezansi). Amanye amagundane adinga ukuvuselelwa kabusha kwe-female 1 kuze kube sekupheleni kwesigaba 5 (n = 3). Izenzo zokubeka u-1 wesifazane ngemuva kwesikrini nokususwa kwesahluko kungenzeka ukuthi sekusebenze njengamaphuzu aphambili okudambisa okuholela ekuqhumeni. Kumele kuqashelwe ukuthi umklomelo we-satiation we-30 min ngaphandle kokusa, nakuba wasetshenziswe ngaphambilini (Ibhishi neJordani, i-1965; Mas et al., 1995b), ihlukumezeka futhi ayinesiqinisekiso sokuthi i-rat ayengeke ifakwe inikezwe isikhathi esengeziwe. Noma kunjalo, ukulibaziseka noma ukususwa nezinqubo zokufaka esikhundleni akuzange kuholele ngokuthembekile ekuqhutshaniseni okuvuselelwe ne-female 1 (isib. Izigaba ze-4 ne-5).

Ithebula 1

Ukuziphatha ngesikhathi sokuhlolwa komphumela we-Coolidge

Wonke amagundane abonise umphumela weCoolidge. Umsebenzi ohlotshaniswa nokubekwa kwe-2 wesifazane ngemuva kwesikrini futhi, ikakhulukazi, ukususwa kwesahluko kungase kube nesandla kulo mphumela, kodwa, futhi, lezi zenzakalo azizange zodwa ngokwanele ukuvuselela ukukopishwa ekuqaleni kokuhlolwa. Ukuqhathaniswa phakathi kwezinyathelo zokuziphatha ngokocansi ne-female 1 kanye ne-female 2 kwenziwa ngokusebenzisa t ukuhlolwa nge-Correction Bonferroni. Yize ukuvama kwezingxenyana nokungahambisani nokuziphendulela ekuphenduleni i-2 yowesifazane akufani neze ngokuphawulekayo kulabo abasemgqeni wokuqala wokuphefumula no-1 wesifazane, ngokujwayelekile, ukuziphatha ngokocansi ne-female 2 kwakungenamandla kakhulu, njengoba kuboniswe ngokuphawulekayo kwe-ejaculations (kusho, i-0.6 no-4.2; F = 49.86;p <0.01) nokungena ngaphakathi (mean = 11.2 vs 37.0;F = 20.17; p <0.05) ngehora lokuqala. Izinombolo zezintaba ehoreni lokuqala nabesifazane 1 no-2 bezingahlukile kakhulu.

Kubalulekile ukuqaphela ukuthi abesifazane abasetshenziswe ngesikhathi se-satiation ingxenye yokuhlolwa (okungukuthi, i-female 1) namanje babonisa ukuqonda okuqinile (isib. Ukugxuma nokushayela) nokuziphatha okulalelayo (ie, lordosis) isikhathi esiphelele sokuxhumana kwabo nendoda .

I-Neurochemistry

Izibalo ze-DA ezincane ezisezingeni eliphansi kanye nama-metabolites alo ezincane ezincane, ezivezwe njenge-mean ± SEM, zamasampula ayisisekelo okuqala amathathu: DA, 3.0 ± 0.7; I-DOPAC, i-619.1 ± 77.7; ne-HVA, i-234.2 ± 49.0 (engahlelelwe ukubuyiswa kweprobe;n = 5). Lezi zindinganiso zimelele izilinganiso eziyisisekelo ze-100%.

Amaphuzu wedatha echazwe ngokuziphatha, ahambisana nesigaba ngasinye sokuhlolwa futhi evamile kuwo wonke amanothi, asetshenziselwa ukuhlaziywa kwe-neurochemical. Lezi zihlanganisa lokhu okulandelayo: (1) amasampuli ayisikhombisa ngemva kokusungulwa kokuqala kwe-female 1, (2) amasampula amane ahambisana nokungabi khona kokuziphatha okukwenziwe nge-female 1, no-3) amasampuli amahlanu emva kokuboniswa kwe-female 2. Umfanekiso 1 ibonisa izinguquko ezingxenyeni ze-DA (igrafu yomugqa, maphakathi) kanye nama-metabolites e-DA (igrafu yomugqa, top) efana nokuziphatha kokuphikisana (ibrafu yebha, phansi) ngesikhathi sokuhlolwa komphumela weCoolidge.

I-Fig. 1.

I-Nucleus ihlangene ne-correlates ye-neurochemical yokuziphatha ngokocansi ngesikhathi somphumela we-Coolidge. Amasampuli ayisishiyagalombili okuqala amelela amaphuzu wedatha aqhubekayo kusukela ngezigaba 1 kuya ku-3. Isibonelo se-1 yisampuli esinesisekelo sokuqala esinesine futhi sokugcina (Bas). Isampula i-2 imelela ukusungulwa kwe-female 1 ngemuva kwesikrini (Isihl). Ngemuva kweminye ye-15, isikrini sisusiwe, futhi amagundane avunyelwe ukulinganisa (amasampuli 3-8). Iukuphuka use x-axis ihambelana nokukhishwa kwedatha kusuka kwamagundane aphethwe isikhathi eside newesifazane wokuqala. Amasampuli ayisishiyagalolunye okugcina nawo aqhubeka ngokulandelana kwesikhathi. Amasampuli i-9 ne-10 afana nenkathi yokukhipha isigaba se-3 (okungukuthi, i-30 min ngaphandle kokukhuphuka). U-1 wesifazane wabe esengena kabusha ngemuva kwesikrini (isampula 11) futhi, emuva kwesikhathi kwe-15, isikrini susiwe (isampula 12). Ngemuva kwe-15 iminithi engenayo ukukopisha, i-2 yowesifazane ibekwe ngemuva kwesikrini (isampula 13). Amasampuli 14-17 afana nokubhekana ne-female 2. Inombolo ye-mounts, intromissions, noma i-ejaculations ehlobene nesampuli ngayinye ye-15 min microdialysis iboniswa ibhafu yebha engezansi. Idatha ye-neurochemical iboniswa ngokwemaphesenti wezingqalasizinda zokuqala. Izinguquko ku-DA ye-NAC (izikwele ezivaliwe), I-DOPAC (imibuthano evaliwe), ne-HVA (imibuthano evulekile) i-efflux ihanjiswa njenge umugqa wamagqa. Ukuqhathaniswa okulandelayo kwenziwa: isampula esisisekelo 1 ngokuhambisana namasampuli 2-10; Isampula esisekelweni esisha 10 ngokuhambisana namasampuli 11 no-12; Isampula esisezingeni eliyisisekelo 12 ngokumelene namasampuli 13-17 (*p <0.05; ** p <0.01). Ezimele t ukuhlolwa kwenziwa phakathi kwamagugu okuqala (amasampula 1, 10, ne-12). Ngokungafani okuphawulekayo kusuka kwesisekelo sokuqala (isampula 1), †p <0.05.

Ukuhlukanisa indlela eyodwa, izinyathelo eziphindaphindiwe ze-ANOVAs zenziwa idatha ye-neurochemical ehlobene ne-female 1 (amasampuli 1-12) ne-2 yabesifazane (amasampuli 12-17). A priori Ukuqhathaniswa kwenziwa ngokusebenzisa ukuhlolwa kokuqhathanisa okuningi kukaDunn (Bonferroni t). Iziqhathaniso ezintathu ezilandelayo eziyinhloko zenziwa: (1) isisekelo sokuqala (isampula 1) ngokuhambisana namasampuli 2-10 (ukuchayeka kokuqala kwe-female 1), (2) isisekelo sesibili (isampula 10) ngokuhambisana namasampuli 11 no-12 (ukuphindaphinda kwe-female 1) , futhi (3) isisekelo sesithathu (isampula 12) ngokumelene namasampuli 13-17 (ukuvezwa kwe-female 2).

Kukhona ushintsho olubalulekile kulo lonke i-DA efflux ekuphenduleni i-female 1 [F (11,44) = 8.48; p <0.001] nowesifazane 2 [F (5,20) = 2.83;p <0.05]. Ukwanda okuphawulekayo kwe-DA efflux kwatholakala lapho owesifazane ongu-1 ekhona ngemuva kwesikrini (+ 44%,p <0.05; isampula 2). Ngesikhathi sokuqhudelana, ukugxila kwe-DA kwanda ngokuqhubekayo, kwafinyelela inani eliphakeme (+ 95%;p <0.01) ngesikhathi sempi yokuqala yokuphoqelela (isampula 3). I-DA ihlale iphakeme kulo lonke ikopisha futhi yabuyela kuphela ekugxilweni okuyisisekelo esikhathini semizuzu engama-30 lapho kungazange kwenzeke khona ukukhuphuka (amasampula 9 no-10). Kungabuyiswa kabusha kwe-1 yowesifazane ngemuva kwesikrini (isampula 11) noma ithuba lokuxhumana ngokomzimba, kepha ngaphandle kokuphakama (isampula 12), ukugxila kwe-DA okuphakeme okuhlobene nenani lesibili lesisekelo (isampula 10). Ukuba khona kwe-2 yabesifazane ngemuva kwesikrini (isampula 13) kuholele ekukhuleni okuncane kwe-DA efflux (12%) kusuka kunani lesisekelo lesithathu (isampula 12) elingafinyelelanga ekubalweni kwezibalo. Ukuvuselelwa okwenziwe kabusha nabesifazane 2 kwaholela ekukhuleni okuphawulekayo (34%) (p <0.05) ku-DA efflux ngesikhathi sokuqala kokulinganisa (isampula 14). Yize ukuziphatha okubuthakathaka kwamakhophi okuqhubekela phambili kumasampuli amathathu alandelayo, izingqinamba ze-DA zehle zaya kumanani ayisisekelo (amasampula 15-17). Ezimele t izivivinyo ezenziwe phakathi kwamasampuli "okuyisisekelo" (okungukuthi, i-1, i-10, ne-12) yabonisa ukuthi lezi zimiso azifani kakhulu.

Kulezi zimpondo ezintathu eziphinde zaqala ukukopisha lapho i-1 yowesifazane ibuyiselwa kabusha, ama-NAC DA akhuphuka lapho i-1 yowesifazane ekhona ngemuva kwesikrini (ububanzi, i-25-47%) futhi ngesikhathi sokuxubana (ububanzi, i-13-37%), ngokuhlobene nesampula nje ngaphambi kokuvuselelwa kabusha kwesifazane. Lokhu kwanda, kodwa kwenzeka kuphela uma ukuziphatha kobulili kwakunamandla futhi kwaholela ekujuleni.

Izinguquko eziphawulekayo jikelele ku-DOPAC [F (11,44) = 9.57; p <0.001] ne-HVA [F (11,44) = 12.47; p Ukutholakala kwe- <0. 001] kutholakale ekuphenduleni kwe-1 yabesifazane, kepha hhayi abesifazane. Ukugxilwa kwe-Metabolite kukhuphuke kancane (+ 2% kuzimo zombili) ngenkathi kwethulwa i-15 yowesifazane ngemuva kwesikrini (isampula 1), kepha lokhu bekungabalulekanga ngokwezibalo. Kube khona, kepha, ukwanda okuphawulekayo kokugxila kwe-DOPAC ne-HVA ngesikhathi sokuqhutshwa (amasampula 2-3), afinyelela amanani aphezulu (+8 kanye + 80%, ngokulandelana; p <0.01) ngemuva kwama-60 min (isampula 6 kuzimo zombili). Yize ukugxila kwe-metabolite kwehle ngesikhathi sokungasebenzi ocansini ekugcineni kokuxhumana nabesifazane be-1 (amasampula 9 no-10), ukugxila kusalokhu kuphakanyisiwe maqondana nesisekelo sokuqala (p <0.05 kuzimo zombili). Ukufakwa kabusha kwe-1 yowesifazane ngemuva kwesikrini (isampula 11), ukufinyelela kwe-1 yowesifazane ngemuva kokususwa kwesikrini (isampula 12), kanye nokwethulwa kwe-2 yabesifazane (isampula 13) akuholelanga kunoma yiziphi izinguquko kokugxila kwe-metabolite. Kancane, kepha kungabalulekile kangako ngokwezibalo, kukwanda kokugxila kwe-DOPAC ne-HVA (+ 23% kuzimo zombili) maqondana nesisekelo (isampula 12) kufana nokuqhutshwa kokuqala kokuqhathwa nabesifazane 2 (isampula 14). Lokhu kwanda kwahlala isikhathi esifushane, noma kunjalo, futhi kwehla kwamanani ayisisekelo amasampuli amathathu asele (15-17). Ezimele tizivivinyo ezenziwa phakathi kwamasampula "okuyisisekelo" (okungukuthi, i-1, i-10, ne-12) ibonise ukuthi amanani ayisisekelo wesibili nesithathu (amasampuli 10 no-12, ngokulandelana), nakuba ahluke komunye nomunye, ahlala ephakanyisiwe kakhulu uma kuqhathaniswa nesampula sokuqala esisekelo i-DOPAC ne-HVA (p <0.05 kuzimo zombili).

Histology

I-Microdialysis probes yayiseNAC (Fig.2) ebangeni elidlulisela + i-1.20 kuya ku-1.70 mm kusuka ku-bregma (i-skull flat). Kukhona ukuhlukahluka futhi kule ndege ye-mediolateral; Idatha ibonisa isampula kusuka egobolondo nasezindaweni eziyinhloko ze-NAC.

I-Fig. 2.

Indawo ye-microdialysis probes ngaphakathi kwe-NAC yamagundane abesilisa asetshenziselwa ukuhlolwa komphumela weCoolidge. Amathanga angama-Shaded ihambelana nendawo evuliwe yesikhumba se-microdialysis probes. Izigaba zobuchopho zengqondo zangasese zahlulwa kusukelaI-Paxinos ne-Watson (1986).

UKUKHULUMA

Ngokuvumelana nemibiko yangaphambilini, imiphumela yamanje ibonisa ukuthuthukiswa kwe-DA yokubukeka kwe-mesolimbic ehambisana nezinkampani eziphazamisayo nezokuphefumula zokuziphatha kobulili lwamaduna njengoba kuhlolwe nguvivo i-microdialysis (Mas et al., 1990; I-Pfaus et al., I-1990;Pleim et al., 1990; Damsma et al., 1992; I-Wenkstern et al., I-1993; I-Fumero et al., I-1994; Mas et al., 1995a,b,d). Ngaphezu kwalokho, le miphumela inikeza i-correlate ye-neurochemical ye-satiation yezocansi kanye nokuvuselelwa okulandelayo kokuphendula ngokuphendukela kwendoda enomuntu owemukelayo (umphumela weCoolidge). Idatha yamanje ibonisa ukuthi izakhiwo zokuvuselela zezinsikazi ezamukelekayo zendabuko zingase zenze ukwandisa ukuhanjiswa kwe-NAC DA kumlingani wesilisa ohlukunyezwa ngokocansi okungenzeka ukuthi uhlobene nokuvuselelwa kokuziphatha ngokobulili. Lokhu kubonakala kuqala ekunyuseni kancane kwe-DA ye-NAC ngenkathi kuboniswa owesifazane omusha ngemuva kwesikrini futhi kwenzeka ngokugqama kakhulu njengokwanda okwenziwe ngokuphindaphindiwe ngesikhathi sokuvuselelwa kokuvuselelwa ne-female 2 (Fig.1).

Ukuba khona kwesifazane wokuqala owamukelayo ngemuva kwesihenqo kwaholela ekunyuseni okunamandla okunamandla ku-DA ye-NAC efflux (i-44% kusuka kwesisekelo) esifana nobukhulu kulokho okwakushiwo ekuhlolweni kwangaphambilini usebenzisa umklamo ofanayo (30%, I-Pfaus et al., I-1990; I-35%,Damsma et al., 1992). Futhi ngokuvumelana nalezi zifundo bekubhekwa ukuthi i-NAC DA efflux yathuthukiswa ngokuqhubekayo ngesikhathi sokukopisha (kuya> 95% ngaphezulu kwesisekelo esivivinyweni samanje). Yize singabuka ukuziphatha okuphelele njengokuhlanganiswa nokukhishwa kwe-NAC DA okuthuthukisiwe (I-Wenkstern et al., I-1993; U-Wilson et al., I-1995), kubalulekile ukuhlola amagama athi "ukucindezela" futhi "ukuphelisa" esimweni sokuziphatha kocansi. Nakuba isigaba lapho owesifazane ekhona khona ngemuva kwesikrini kuwukuphela kokuncintisana noma ukulungiselela, ukuziphatha ngesikhathi sesigaba sokukopisha akunakucatshangwa njengokwedlulele. Ngoba "ukuncintisana" kungasetshenziselwa ukuchaza konke ukuziphatha okuholela ekuqedeni kokuziphatha okugqugquzelayo (ukukopiselana), ukuziphatha okuyisisekelo umbukiso wesilisa ngenkathi usebenza esigabeni "sokuphelisa" okuchazwa kangcono njengokwenzakala; owesilisa uchitha isikhathi esiningi kanye nomzamo ukuphishekela owesifazane ukuba alandele. Kule ndaba, singalinganisa ukuhanjiswa okukhulu kwe-NAC DA nokuphelisa kanye ne izingxenye ezicindezelayo kakhulu zokuziphatha komuntu wesilisa ngokocansi.

Ukufinyelela kwesibili, insikazi yowesifazane yenze ukuba kuqhutshekwe ukukopisha kuzo zonke izihloko. Ucwaningo lwangaphambili lubonise ukuthi iningi lamakhompi avunyelwe ukuba alandele ukungahlali, esebenzisa isenzo esifanayo sokuziphatha okusetshenziselwa ukuhlolwa okwamanje, akazange aqhubeke nokuxubana lapho ehlolwa i-24 hr kamuva (Ibhishi neJordani, i-1956). Kungenzeka ukuthi ukutholakala kwezakhiwo ze-novel stimulus ze-2 yowesifazane, okungenzeka ukuthi zazibandakanya ama-olfactory kanye namazwi abukwayo nokuhlola, kwaholela ekuqhutshweni kokuvuselelwa. Umbuzo othakazelisayo, ozohlala uphendulwa, yiyiphi indlela umlingo wesilisa ohlukanisa ngayo owesifazane onomuntu ovela kumfazi awakhulume naye maduzane. Isayithi laleyo ndlela ingase isetshenziswe ohlelweni oluyinhloko. Kuye kwabikwa ukuthi ubuqotho balesi simiso kubalulekile kumphumela we-Coolidge kuma-hamsters (UJohnston noRasmussen, i-1984). Uhlelo lwe-vomeronasal-accessory system, kodwa, lapho inqubo yememori ye-pheromonal ichazwe maduzane emasimini (Kaba et al., 1994), uyiphakamiso esiphezulu. Kulokhu, kuyaphawuleka ukuthi ukunyuka kokudluliselwa kwe-NAC DA kwalinganiswa ukusetshenziswa vivo i-voltammetry emathongwini abesilisa abekwe embhedeni owavezwa amazinyokazi e-estrus (Louillot et al., 1991; UMitchell noGratton, i-1992). Ngaphezu kwalokho, ukusetshenziswa K+ ngqo ungqimba lwezintambo ze-vomeronasal we-accessory ibha ye-bulb, kanye ne-accessory ye-bulb elfactory ngokwayo, okwanele ukwandisa ukuhanjiswa kwe-NAC DA (UMitchell noGratton, i-1992).

I-15 min yokuphelelana kokuqala kokubambisana ne-female 2 yayihlotshaniswa nokunyuka okukhulu kwe-NAC DA. Ngokungafani ne-1 yowesifazane, ukusebenzisana ne-female 2 akuzange kwenzeke ukwanda kwe-DA ye-NAC yezinga elifanayo ngesikhathi sokuncintisana (12%) noma ukuphazamiseka (34%) izigaba. Lokhu kwanda okuncane eNDA ye-NAC, noma kunjalo, kuyahambisana kahle nezinga elincishisiwe lokuziphatha ngokocansi eliboniswe ne-female 2 uma kuqhathaniswa ne-female 1. Ama-metabolite concentrations ahlala ephakama ngesikhathi sesisindo, okwenza kube nezinhlawulo ezintsha (amasampula 10 no-12) aphakanyisiwe kakhulu kusukela ekuqaleni kwesilinganiso sokuqala (isampula 1).

Ukwehla okwesikhashana okwenyuka kwezinguquko ze-DOPAC ne-HVA ngenkathi kuqubuzana kuhambisana nokubunjwa kwawo njenge-metabolites yenkampani yomzali, i-DA. Kuye kwaphakanyiswa ukuthi izingxube ze-microdialysis ze-metabolite, okungenani ngesikhathi sokuziphatha kwemvelo okungenayo i-pharmacologically eqhutshwayo, inikeza inkomba ewusizo yomsebenzi we-neural (Damsma et al., 1992; I-Fumero et al., I-1994). Iqiniso lokuthi izingxube ze-metabolite zahlala ziphakanyisiwe ngisho nangezinkathi zokungasebenzi ngokocansi kulokhu kuhlolwa, lapho ama-concentrations e-DA ebuyisele ukuzitshengisa amanani ayisisekelo, abeka ukungabaza ngalesi siphakamiso.

Ukuphakama okuqhubekayo kwama-metabolite e-DA aboniswe kulezi zibuko zokuhlola indawo yomphakathi yangaphambili (mPOA) ye-metabolite ye-DA ekhonjwe ngamagundane ngosuku lokuqala emva kokuba ilandelanise nesifo (satiation)Mas et al., 1995a,b). Ukuphakama okuqinisekisiwe kwezingqikithi ze-DOPAC ne-HVA ku-NAC noma i-mPOA azigcinwa ngaso sonke isikhathi lapho isikhathi sokulinganisa singesikhathi esinqunyiwe, esifushane kakhulu kunesikhathi esidingekayo ukuze sifinyelele ukukhathala. Isibonelo, ucwaningo oluningi lubonise ukuthi izingxenyana ze-DOPAC zanda futhi zahlala ziphakanyisiwe ngesikhathi sokuqhuma kodwa zanqabela amanani ayisisekelo ngemuva nje kokuba owesifazane asuswe (I-Pfaus et al., I-1990; Pleim et al., 1990; Damsma et al., 1992;Hull et al., 1993; I-Wenkstern et al., I-1993; Hull et al., 1995). Esifundweni Mas et al. (1995b), ama-concental extraallular concentrations we-DOPAC ne-HVA ku-mPOA ahlala ephakeme ngaphezu kwezinsuku ezingu-4 ezilandelanayo ezihambisana nesikhathi sokungasebenzi ngokocansi. Ngosuku lwesine, ngaphambi nje kokuba izilwane ziphinde ziqalise ukukopishwa, izingxenyana ezisisekelo ze-metabolites zazisondelene nemigomo yokulinganisa. Abalobi bafanisa iphethini lezinguquko ze-neurochemical kulabo ababonwayo emva kokuphathwa kwe-DA receptor blockers (Zetterström et al., 1984; Imperato noDiChiara, i-1985) futhi basikisela ukuthi isimo sokungasebenzi kwezocansi singaphikisana nge-prolactin ukukhululwa, okungase kube "yi-neuroleptic engapheliyo" (Mas et al., 1995a,b,d). Kuyacaca ukuthi ukuphathwa kwe-neuroleptic kuhambisane nokunyuka kwezingxube ze-metelollar extracellular kanye ne-DA efflux (Zetterström et al., 1984; Imperato noDiChiara, i-1985). Ngeshwa, Mas et al. (1995a,b) abakwazanga ukuthola ukuthi yi-MPOA DA. Esifundweni samanje, izingxube ze-DA ku-NAC zibuyele kumanani wokubala, kuyilapho i-DOPAC ne-HVA izikhala zihlala ziphakanyisiwe. Leli phethini alihambisani nendima ye-neuroleptic ehlala njalo e-NAC ukuze kuqhutshwe isifo socansi.

Njengoba kunikezwe ukubandakanyeka kwama-neurons e-DA e-mesolimbic ngokuziphatha okukhuthazayo (Fibiger noPhillips, i-1986; I-Blackburn et al., I-1992; Kalivas et al., 1993; LeMoal, i-1995) nokuzwela kwabo kwenzalo yendawo yemvelo (I-Fabre et al., I-1983; I-Schultz, i-1992; Mirenowicz no-Schultz, i-1994), ukwanda okwenziwe emazingeni angaphandle kwe-NAC DA ngokuphendula owesifazane wamanoveli kuyavumelana nenkolelo yokuthi umsebenzi kule system ye-DA ibalulekile ekuvuseleleni ukuziphatha ngokocansi. Ngaphezu kwalokho, imibiko yokukhushulwa nokucindezela kokudluliswa kwe-DA (Hull et al., 1993, 1995;Mas et al., 1995b; Sato et al., 1995) nomsebenzi we-neuronal (Shimura et al., 1994) ku-mPOA yamagundane wesilisa phakathi nokuziphatha kobulili kusikisela ukuthi lesi sakhiwo singase sibe nomthelela ekuhloliseni okuhlangenwe nakho kohlobo lwe-Coolidge.

Ngokuhambisana nendima ebanzi yesistimu ye-DA ye-mesolimbic ngokuziphatha okugqugquzelayo, kusungulwe kahle ukuthi ama-extracellular concentrations we-DA nawo aphakanyisiwe ngaphambili, ngesikhathi, futhi ngemuva kokudla kokudla, ngokubuyela emuva kumagugu okuqala ~ okungenani okungenani kwe-30 (U-Wilson et al., I-1995). Kuyaziwa kahle ukuthi ukuphazamiseka okubangelwa ukudla kuthonywa izakhiwo zayo zokuzwa. Abantu nezilwane bayenqaba ukudla abadla ngakho ukuze baphuze futhi badle ukudla okungazange kudliwe (I-Rolls, i-1986). Lokhu kuphakamisa umbuzo wokuthi ngabe i-extracellular DA efflux ku-NAC izokwenyuka ngokukhetha ngokuletha uhlobo lokudla olusha, kodwa hhayi ngokudla okudliwe maduzane ukuze kuhlaselwe ngendlela efana nalokhu okubikiwe esifundweni samanje kumongo isisusa socansi. Uma kuqinisekisiwe, lobu buhlobo obuvamile phakathi kwezakhiwo ezizwakalayo zomvuzo wemvelo, i-satiety, ne-mesolimbic ukudlulisa i-DA kuzodala indima ebalulekile kule nqubo ye-neural ekulawulweni kwezinqubo zokugqugquzela, ukuphazanyiswa okungabangela ukuphazamiseka okukhulu kokudla nokusebenza ngokobulili .

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