Dynamics Release Dynamics Gbanwee n'oge na-eto eto na mgbe mmanya afọ ofufo (2014)

A na-ejikọta oge uto na nnukwu mkpali na ịṅụ ihe ize ndụ, na-eme ka ndị nọ n'afọ iri na ụma nwee mmasị iji ọgwụ ọjọọ eme ihe. Ejikọtara iji ọgwụ mbụ eme ihe na ihe ize ndụ dị ukwuu maka nsogbu iji ihe eme ihe na ndụ ma emesịa na usoro neurobiological amabeghị. Ụbụrụ na-enwe ọganihu dị ukwuu n'oge uto na ọgba aghara n'oge a ka a na-eche na ọ ga-enye aka n'ịbawanye adịghị ike. Mgbanwe site na njikwa na iji ọgwụ mmanye na riri ahụ gụnyere mgbanwe na-adịte aka na netwọkụ akwara gụnyere ngbanwe site na nucleus accumbens, na-eme ka mmetụta na-agba ume siri ike, na-ewebata striatum dorsal na nhazi omume. Ọmụmụ ihe a bụ iji nwalee echiche nke mmụba dopamine ntọhapụ mgbe ihe ịma aka ọgwụ na oke na-eto eto gasịrị. A nyochara ntọhapụ na nnabata nke potassium na-enweta site na iji ndekọ nke chronoamperometric dopamine yana ihe ịma aka sitere na amphetamine na mmalite na mbubreyo oke oke na oke oke. Na mgbakwunye, a nyochara nsonaazụ nke ị alcoholụbiga mmanya ókè n'oge uto na mmetụta ndị a. Ihe omuma a gosiputara mmụba nke nta nke nta nke ntọhapụ dopamine na afọ, na-akwado ọmụmụ ndị gara aga na-atụ aro na ọdọ mmiri nke dopamine na-ewepụta na-abawanye na afọ. N'ụzọ dị iche, a na-ahụ mbelata nke nta nke nta nke ntọhapụ na afọ na nzaghachi nke amphetamine, na-akwado nnukwu nchekwa nchekwa nke dopamine na ụmụ anụmanụ na-eto eto.. Usoro Dopamine mgbe ịṅụ mmanya na-egbu onwe ya mere ka mwepu ntọhapụ dị ala na nzaghachi na potassium-chloride, na-egosi na mmanya na-emetụta ọdọ mmiri nke dopamine na nke a nwere ike inwe mmetụta maka adịghị ike na ịṅụ ọgwụ ọjọọ na nchọpụta ọrịa uche ndị ọzọ metụtara dopamine na dorsal striatum.

Akụrụngwa na ụzọ

Nkwupụta Ụkpụrụ

Emere nnwale anụmanụ niile n'okpuru ụkpụrụ nke Kọmitii Ethical Animal Uppsala kwadoro wee soro ntuziaka nke Swedish Legislation on Animal Experimentation (Animal Welfare Act SFS1998: 56) na European Communities Council Directive (86/609/EEC).

Animals

Oke Wistar dị ime (RccHan: WI, Harlan Laboratories BV, Horst, Netherlands) rutere n'ụlọ anụ ụlọ n'ụbọchị ime ime 16. Anụmanụ ahụ rutere n'ọkwa ihe karịrị izu ole na ole ka ha wee nabata oge nke ndekọ chronoamperometric. A na-edobe ihe mgbochi mmiri n'otu oghere macrolon (59cm × 38 cm × 20 cm) na nri pellet (Ụdị R36; Lantmännen, Kimstad, Sweden) na mmiri mgbata. ad libitum. Ngwongwo ndị ahụ nwere ihe ndina osisi na mpempe akwụkwọ (40×60; Cellstoff, Papyrus) ma ndị ọrụ na-ahụ maka anụmanụ na-agbanwe otu ugboro n'izu. A na-edobe ọnụ ụlọ anụmanụ na okpomọkụ mgbe niile (22± 1°C) na iru mmiri (50± 10%) na ọkụ 12 h mgbe niile na okirikiri gbara ọchịchịrị na ọkụ na 06:00 am. Ime ụlọ niile nwere mkpọtụ n'azụ mechiri emechi iji belata ụda a na-atụghị anya ya nke nwere ike inye ụmụ anụmanụ nsogbu.

Enwere ike ịchọta nchịkọta nke ndepụta nnwale na Nyocha 1. A na-akwalite ihe mkpofu ndị a mụrụ n'otu ụbọchị ahụ (ụbọchị postnatal (PND) 0) gụnyere ụmụ nwoke 6 na ụmụ nwanyị 4 iji chịkwaa nrụgide mbupu nke nne, omume nne na mkpụrụ ndụ ihe nketa. A gbapụrụ ụmụ ọhụrụ ara na PND 22 wee debe 3 kwa ọnụ ụlọ ruo mgbe PND 28 (± 1 ụbọchị) ma ọ bụ PND 42 (± 1 ụbọchị) mgbe emere ndekọ chronoamperometric. Ọ bụ naanị ụmụ nwoke ka a ga-eji mee ihe n'ọmụmụ ihe a. Enyere otu oke oke iri atọ na afọ afọ ofufo ohere dị ka 20% ethanol n'ụdị nhọrọ nhọrọ karama abụọ sitere na PND28 ruo PND65. E nyere ụmụ anụmanụ ahụ awa iri abụọ na anọ ohere ịnweta ethanol ụbọchị atọ n'usoro kwa izu, ya bụ Tuesday ruo Tọzdee maka izu isii, ngụkọta nke nnọkọ iri na asatọ. Maka ọ̀tụ̀tụ̀ oriri ethanol, a tụrụ karama ndị ahụ tupu na mgbe nnọkọ ọ bụla gasịrị, a na-agbakọkwa gram dị ọcha ethanol kwa kilogram ịdị arọ ahụ. A gbanwere ọnọdụ karama n'etiti nnọkọ iji zere mmasị ọnọdụ. A na-edobe anụmanụ ndị na-aṅụ mmanya ethanol n'otu n'otu site na PND 24 ruo PND 18. A na-ahọrọ anụmanụ ndị nwere ọnụ ọgụgụ ethanol kachasị elu (g / kg) na ndekọ electrochemical na PND 28 (± 70 ụbọchị). A na-edobekwa njikwa ịṅụ mmiri nke dabara na ya n'otu n'otu n'otu oge ahụ.

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Ọgụgụ 1. Ihe ngosi nnwale.

E = mmanya ethanol, PND = ụbọchị ọmụmụ, W = ịṅụ mmiri.

a: 10.1371 / journal.pone.0096337.g001

Ndekọ Chronoamperometric nke Dopamine In vivo

Akụrụngwa.

Inactin, Nafion 5% ngwọta, dopamine hydrochloride, L-ascorbic acid, potassium chloride, sodium chloride, sodium phosphate, calcium chloride na d-amphetamine sulfate nwetara site na Sigma-Aldrich, LLC (St Louis, MO, USA). E nwetara Kerr sticky wax site na DAB LAB AB (Upplands Väsby, Sweden). Carbon fiber microelectrodes (SF1A; 30 µm mpụta dayameta × 150 µm ogologo) zụtara na Quanteon, LLC (Nicholasville, KY, USA), a zụtara waya ọlaọcha electrode (200 µm, Teflon-mkpuchi) sitere na AM Systems Inc. Carlborg, WA, USA) na iko capillaries (0.58 mm n'ime dayameta) maka micropipettes ka zụtara n'aka World Precision Instruments Ltd (Stevenage, UK).

Ịwa ahụ.

Emere ndekọ Dopamine na PND 28 (± 1 ụbọchị), PND 42 (± 1 ụbọchị) ma ọ bụ PND 70 (± 2 ụbọchị). A rụrụ ịwa ahụ ozugbo tupu e dekọọ ihe ndekọ electrochemical. A na-eji ihe mkpuchi ọkụ na-ekesa mmiri (Gaymar Industries, Inc., Orchard Park, New York) iji kwado okpomọkụ ahụ. Ejiri Inactin 125 mg/kg intraperitoneally (ip) na-egbu anụ ahụ ma tinye ya na stereotaxic frame (Stoelting Co., Wood Dale, IL, USA). A kụpụrụ oghere dị n'okpokoro isi na-ekpuchi ebe a na-edekọ maka electrode ahụ, na oghere ọzọ gbapụrụ n'ebe dịpụrụ adịpụ site na ebe ndekọ maka ntinye nke Ag/AgCl reference electrode.

Ndekọ chronoamperometric dị elu nke ntọhapụ na nnabata dopamine.

Emere nha chronoamperometric dị elu (ọnụego nlele 1 Hz, mkpokọta 200 ms) site na iji sistemụ ndekọ FAST16-mkII (Fast Analytical Sensing Technology, Quanteon, LLC, Nicholasville, KY, USA) dịka usoro akọwara na mbụ. [16]. Carbon fiber microelectrodes (SF1A) ejiri mkpuchi Nafion atọ kpuchie ya na 5 min kpo oku na 200 Celsius tupu mkpuchi nke mbụ na mgbe mkpuchi ọ bụla gasịrị. [17]. A na-ahazi electrodes ahụ na vitro na 0.05 M phosphate buffered saline iji chọpụta selectivity, njedebe nke nchọpụta (LOD) na mkpọda tupu eji. na vivo [16]. Microelectrodes gosipụtara nzaghachi ahịrị na mgbakwunye nsonye nke dopamine (2-6 µM), yana ngụkọ mmekọrịta (R2) nke 0.999± 0.0003. Nkezi nhọrọ maka elektrọd niile ejiri na ọmụmụ a bụ 14482 ± 3005 µM maka dopamine karịa ascorbic acid. Nkezi LOD bụ 0.026 ± 0.004 µM dopamine, na nkezi mkpọda bụ -1.00± 0.03 nA/µM dopamine. Nkezi mbelata/oxidation ratio tụrụ n'oge nzaghachi kacha elu nke dopamine bụ 0.67± 0.02, nke na-egosi nchọta nke dopamine kachasị. [17]. A na-etinye waya ọlaọcha ma jiri ya mee ihe na vivo Ag/AgCl ntụaka electrode [18].

Na vivo nnwale protocol.

Ajuju micropipette (10-15 µm n'ime dayameta) na isotonic potassium chloride solution (120 mM KCl, 29 mM NaCl, 2.5 mM CaCl₂· 2H₂O) (pH 7.2-7.4) na-eji agịga na-ejuputa pipette (28G, World Precision Instruments, Aston, UK). Edebere micropipette ihe dịka 150-200 µm site na ọnụ ọnụ eriri carbon site na iji waks na-egbuke egbuke. A na-etinye electrode na stereotactically na dorsal striatum, AP: +1.0 mm, L: +3.0 mm site na bregma, a na-edozi mmanya incisor dịka afọ na ịdị arọ si dị. [19], [20]. Edobere elektrọd ahụ na mbụ azụ azụ (-3.0 mm) na saịtị ndekọ ahụ, na-eji micromanipulator (Narishige International Ltd, London, UK) wetuo ya, ma kwe ka ọ rute n'ụkpụrụ kwụsiri ike maka ihe dị ka 45–60 min tupu ebutu ya na omimi nke -4.0 mm site na bregma. A na-ahapụkwa electrode ọzọ 5–10 min ka ọ kwụsie ike na saịtị ndekọ tupu ekpebie mmetụta nke otu ịgba ọgwụ potassium chloride na mwepụta dopamine. A na-etinye ihe ngwọta potassium na mpaghara site na iji nrụgide nrụgide nke PicoSpritzer III (Parker Hannifin Corporation, Pine Brook, NJ, USA) na-achịkwa na nrụgide (10-20 psi) na oge (0.5-1.0 s) na-edozi iji nyefee 100 nl nke. ngwọta potassium, nke a tụrụ site na microscope ịwa ahụ nke dabara na reticule anya [21].

A na-eji ntọhapụ nke Potassium ewepụtara na ngwakọta nke subcutaneous injections nke amphetamine ma ọ bụ saline. Emepụtara ọnụ ọgụgụ ntụaka atọ yiri ya na njupụta, nkeji iri dị iche. Nkeji ise mgbe ọnụ ọgụgụ ikpeazụ gachara, a na-enye oke ma ọ bụ 10 mg/kg amphetamine ma ọ bụ nha saline (2 ml / kg) na mgbe ahapụchara 1 min ọzọ ewepụrụ ọzọ kwa nkeji 5 ọ bụla, na-emepụta ọnụ ọgụgụ kacha elu na 10, 5, 15. , 25, 35, 45 na 55 min mgbe ịgba ọgwụ mgbochi ahụ gasịrị, lee Nyocha 2A maka akara nnọchite anya. A họọrọ dose nke amphetamine dabere na mmetụta omume na ọmụmụ ihe nchịkwa na nchịkwa onwe onye [22]-[24].

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Onyonyo 2. Ihe nnochite anya.

A) Ihe nnọchi anya nke oxidation ugbu a maka oke na ụbọchị ọmụmụ 28 na-anata amphetamine na B) nso nso nke ọnụ ọgụgụ ntụaka nke abụọ maka otu anụmanụ na-egosi ka esi gbakọọ njupụta na T80. Amp = njupụta, Base = ntọala, Ref = ntụaka.

a: 10.1371 / journal.pone.0096337.g002

Nkwenye nke ntinye electrode na mwepu.

Ebipụrụ electrodes ndị ahụ ma hapụ ya ka ha mechaa nnwale na ụbụrụ jụrụ oyi. Achọpụtara ndobe ahụ site na ngalaba nke ụbụrụ oyi kpọnwụrụ akpọnwụ. Site na anụmanụ iri na abụọ dị na PND12, ewepụrụ 28 n'ihi ntinye na-ezighi ezi, yana 1 n'ihi njehie ndekọ. Maka anụmanụ iri na abụọ ahụ dị na PND 2, e wepụrụ anụmanụ 12 n'ihi ntinye na-ezighi ezi. Maka anụmanụ iri na isii na PND 42, 1 ewepụrụ n'ihi njehie ndekọ. Maka anụmanụ 16 na-aṅụ ethanol na PND 70, 3 ewepụghị n'ihi njehie ndekọ. Njehie ndekọ na-agụnye mkpọchi pipette na ọgba aghara ọkụ eletrik dị ka mbelata ọkụ na ọgba aghara nke ọkụ izugbe na mpaghara ndekọ.

Nyocha data.

A gbakọrọ ọnụ ọgụgụ kachasị elu nke ọnụ ọgụgụ ndị a kpalitere na oge maka ọnụ ọgụgụ kasị elu ga-agbada ruo 80% nke njupụta ya (T80) site na iji ngwa ngwa nyocha FAST 4.4 (Quanteon, LLC, Nicholasville, KY, USA), lee. Nyocha 2B maka akara nnọchite anya. A na-agbakọ ọnụ ọgụgụ kacha elu atọ ndị a ma gbakọọ pasent nke ọnụ ọgụgụ ndị a maka ọnụ ọgụgụ kasị elu na-eso ịgba ọgwụ. Maka nyocha ọnụ ọgụgụ, a na-eji nyocha nke variance ugboro ugboro (ANOVA) atụnyere data chronoamperometric n'ime oge n'etiti afọ ma ọ bụ otu mmanya na ọgwụgwọ (saline ma ọ bụ amphetamine), na-esote Fisher's least significant difference (LSD) ule post-hoc. Maka data oriri ethanol, nke a na-ekesaghị, a na-eji Friedman ANOVA mee ihe. Emere nyocha ndekọ aha site na iji Statistica 10 (StatSoft Inc., Tulsa, OK, USA). A tụlere ndịiche dị ka ọnụ ọgụgụ dị mkpa na p<0.05.

Results

Mmetụta dabere afọ

E gosipụtara ndịiche na njupụta ntụaka dị n'etiti otu afọ Nyocha 3. Usoro ANOVA ugboro ugboro na-atụnyere afọ na oge, gosipụtara mmetụta dị ukwuu nke afọ [F(2,22) = 5.81; p = 0.009], ma enweghị mmetụta nke oge [F (2,44) = 1.43; p = 0.25] ma ọ bụ mmetụta mmekọrịta ọ bụla n'etiti oge na afọ [F (4,44) = 1.70; p = 0.17.

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Ọnụọgụ 3. Ntụaka ọnụ ọgụgụ kachasị elu na afọ dị iche iche.

Amplitudes (µM) (pụtara ± SEM) nke ọnụ ọgụgụ ntụaka atọ ahụ tupu ọgwụgwọ na amphetamine ma ọ bụ saline na ọgbọ atọ; ụbọchị ọmụmụ (PND) 28, 42 na 70. ** p<0.01.

a: 10.1371 / journal.pone.0096337.g003

Enweghị mmetụta nke afọ [F (2,24) = 1.02; p = 0.38], oge [F (2,48) = 0.94; p = 0.40] ma ọ bụ oge na afọ [F (4,48) = 0.22; p = 0.93] ka ahụrụ maka ụkpụrụ ntụnye aka T80. Njehie ọkọlọtọ ± pụtara nke T80 pụtara (SEM) bụ 17.3 ± 1.3 maka PND 28, 19.5 ± 0.9 maka PND 42 na 20.5 ± 1.0 maka PND70.

E gosipụtara ọdịiche dị n'etiti ndị ọgbọ na nzaghachi njupụta na amphetamine Dee 4A-C. Ọgwụgwọ Amphetamine mere ka ọ bụrụ isi mmetụta nke afọ [F (2,26) = 3.95; p = 0.03], ọgwụgwọ [F (1,26) = 10.77; p = 0.003] na oge [F (6,156) = 3.32; p = 0.004], na mmetụta mmekọrịta n'etiti oge na afọ [F (12,156) = 2.23; p = 0.01], oge na ọgwụgwọ [F (6,156) = 4.20; p <0.001], ma ọ dịghị mmekọrịta n'etiti afọ na ọgwụgwọ [F (2,26) = 2.37; p = 0.11] ma ọ bụ oge, afọ na ọgwụgwọ [F (12,156) = 0.77; p = 0.68.

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Ọgụgụ 4. Amplitudes na T80 nzaghachi n'ime oge na afọ dị iche iche.

Nzaghachi n'ime oge mgbe subcutaneous (sc) injections nke saline ma ọ bụ amphetamine, dị ka pasent nke ụkpụrụ ntụaka (pụtara ± SEM), maka amplitudes na A) ụbọchị ọmụmụ (PND) 28, B) PND 42 na C) PND 70, na maka ụkpụrụ T80 na D) PND 28, E) PND 42 na F) PND 70. * p <0.05, ** p <0.01, *** p <0.001 tụnyere njikwa saline, ^#p <0.05 ma e jiri ya tụnyere oge nhata na PND 42, °p <0.05, ° p <0.01, ° ° p <0.001 ma e jiri ya tụnyere oge nhata na PND 70, ^§p<0.05, ^§§p<0.01, ^§§§p <0.001 ma e jiri ya tụnyere oge nhata na PND 28.

a: 10.1371 / journal.pone.0096337.g004

A na-egosi nzaghachi T80 na amphetamine Ihe osise 4D – E. Enweghị isi mmetụta nke afọ [F (2,25) = 1.87; p = 0.17], ma enwere mmetụta nke ọgwụgwọ [F (1,25) = 26.52; p<0.001], oge [F (6,150) = 7.70; p <0.001] na mmetụta mmekọrịta nke oge na ọgwụgwọ [F (6,150) = 12.29; p <0.001]. Enweghị mmekọrịta dị n'etiti afọ na ọgwụgwọ [F (2,25) = 1.29; p = 0.29], oge na afọ [F (12,150) = 0.66; p = 0.78] na omume na-eme ka mmekọrịta dị n'etiti oge, afọ na ọgwụgwọ [F (12,150) = 1.60; p = 0.098.

Ịṅụ mmanya na-aba n'anya n'oge ntorobịa afọ ofufo

E gosipụtara data oriri ethanol maka oke iri na anọ ejiri na ndekọ chronoamperometric. Isiokwu 1. Otu Friedman ANOVA egosighi nnukwu ọdịiche dị na oriri n'ime oge, n'agbanyeghị na enwere usoro [χ² = 9.80; p = 0.08] n'ebe ndịiche na-ebute site na oriri n'ime izu nke abụọ (PND 35-37), nke dị ntakịrị elu karịa izu ndị na-esote. Otu Friedman ANOVA nke mmasị gosiri mmụba ka oge na-aga [χ² = 19.7; p = 0.001], tumadi n'ihi mmụba n'ime izu atọ mbụ, lee Isiokwu 1.

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Tebụl 1. Ihe nrịbama, nke kacha nta na ịṅụ mmanya na-aba n'anya (g / kg / 24 h) na mmasị (%) maka izu isii nke ịṅụ mmanya na-aba n'anya na etiti, nke kacha nta na nchịkọta kachasị (g) mgbe oge 18 gasịrị.

a: 10.1371 / journal.pone.0096337.t001

E gosipụtara ọdịiche dị na njupụta ntụaka n'etiti ethanol- na otu ndị na-aṅụ mmiri Nyocha 5. Usoro ANOVA ugboro ugboro na-atụnyere otu mmanya na oge, gosipụtara mmetụta bụ isi nke otu mmanya [F(1,17) = 16.22; p <0.001], ma enweghị mmetụta nke oge [F (2,34) = 1.76; p = 0.19] ma ọ bụ mmetụta mmekọrịta ọ bụla n'etiti oge na otu mmanya [F (4,44) = 1.32; p = 0.28.

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Ọnụọgụ 5. Ntụaka ọnụ ọgụgụ kachasị elu na mmiri ma ọ bụ ethanol na-aṅụ anụmanụ.

Amplitudes (µM) (pụtara ± SEM) nke ọnụ ọgụgụ ntụaka atọ ahụ tupu ọgwụgwọ ya na amphetamine ma ọ bụ saline n'ime mmiri- na mmanya mmanya ethanol. ** p<0.01, ***p<0.001.

a: 10.1371 / journal.pone.0096337.g005

Enweghị mmetụta nke otu mmanya [F (1,18) = 0.04; p = 0.85], oge [F (2,36) = 1.96; p = 0.16] ma ọ bụ oge na otu mmanya [F (2,36) = 0.22; p = 0.81] ka achọtara maka ụkpụrụ ntụnye aka T80. Ihe ntụgharị ± SEM ntụaka T80 bụ 20.5 ± 1.0 maka oke mmiri na-aṅụ mmiri, yana 19.1 ± 1.3 maka oke mmanya ethanol.

A na-egosipụta nzaghachi na amphetamine na ethanol- na otu ndị na-aṅụ mmiri Nyocha 6. Maka amplitudes, dị ka egosiri na Nyocha 6A, enwere mmetụta na mmetụta nke ọgwụgwọ [F (1,19) = 3.01; p = 0.099] na enwere mmetụta bụ isi nke oge [F (6,114) = 2.30; p = 0.04], mana enweghị mmetụta nke otu mmanya [F (1,19) = 0.39; p = 0.54] ma ọ bụ mmetụta mmekọrịta ọ bụla n'etiti ọgwụgwọ na otu mmanya [F (1,19) = 0.83; p = 0.37] ma ọ bụ oge na ọgwụgwọ [F (6,114) = 1.13; p = 0.35], oge na otu mmanya [F (6,114) = 0.44; p = 0.85] ma ọ bụ oge, ọgwụgwọ na otu mmanya [F (6,114) = 0.27; p = 0.95.

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Ọnụ ọgụgụ 6. Amplitudes na T80 nzaghachi na oge na mmiri-ma ọ bụ ethanol-aṅụ anụmanụ.

Nzaghachi n'ime oge mgbe subcutaneous (sc) injections nke saline ma ọ bụ amphetamine, dị ka pasent nke ụkpụrụ ntụaka (pụtara ± SEM), maka A) amplitudes na B) ụkpụrụ T80 na mmiri (W) - ma ọ bụ ethanol (E) - mmanya dị iche iche. . * p<0.05, **p<0.01, ***p<0.001 tụnyere njikwa saline.

a: 10.1371 / journal.pone.0096337.g006

Maka ụkpụrụ T80, Nyocha 6B, enwere mmetụta isi nke ọgwụgwọ [F (1,19) = 17.35; p <0.001] na oge [F (6,114) = 2.42; p = 0.03], na mmetụta mmekọrịta n'etiti oge na ọgwụgwọ [F (6,114) = 10.28; p <0.001]. Enweghị mmetụta nke otu mmanya [F (1,19) = 0.33; p = 0.57], ma ọ bụ mmetụta mmekọrịta ọ bụla n'etiti ọgwụgwọ na otu mmanya [F (1,19) = 0.76; p = 0.40], oge na otu mmanya [F (6,114) = 1.66; p = 0.14], ma ọ bụ oge, ọgwụgwọ na ịṅụ mmanya [F (6,114) = 1.75; p = 0.12.

Nkwurịta

Achọpụtara mmetụta dabere na afọ na mwepụta dopamine na nnabata n'okpuru ọnọdụ basal yana nzaghachi amphetamine na mmalite na mbubreyo ntorobịa, yana okenye, oke. A tụlekwara mmetụta mmanya na-aba n'anya n'oge uto ma bụrụkwa, dịka anyị maara, ọmụmụ nke mbụ na-enyocha ntọhapụ na iwelite oke mmanya na-eto eto nke nwere usoro chronoamperometric.

Mmetụta dabere afọ

Esemokwu dabere na afọ na njupụta ntụaka kwekọrọ na ọmụmụ gara aga site na iji voltammetry yana mgbakwunye ọkụ eletrik, nke gosipụtara na oke oke toro eto wepụtara dopamine karịa mkpali karịa ụmụ oke oke. [12]. Oge oge uto nke Stamford (1989) ji mee ihe bụ ihe dịka PND 30, mana kemgbe ahụ ọmụmụ egosila na gburugburu PND 40-45 enwere ọnụ ọgụgụ kasị elu na ọkwa basal extracellular nke dopamine. [25]-[27] na dopamine receptor D₂ njupụta [28], ebe ọkwa tyrosine hydroxylase dị ala karịa ma n'oge uto na okenye [29]. Ya mere ọmụmụ ihe ugbu a gụnyere oge abụọ n'oge uto, PND 28 na PND 42, nke kwekọrọ na mmalite na mbubreyo ntorobịa. [11]. Mmụba n'ime anụmanụ ndị nọ n'afọ iri na ụma dị n'etiti ruo n'ogo n'oge uto na ntozu, na-egosi na mmepe site na oge uto ruo n'ịbụ okenye gụnyere mmụba nwayọọ nwayọọ na ikike ntọhapụ nke dopamine na nzaghachi na potassium chloride na dorsal striatum. Nke a kwekọrọ na akụkọ banyere mmụba nke ọkwa dopamine extracellular na nucleus accumbens n'oge okenye ma e jiri ya tụnyere oge uto. [30], [31]. Dịka ekwuru na mbụ, ụfọdụ ọmụmụ na-egosikwa ọkwa kacha elu na PND 45 [25]-[27] na ha nwere ike ime ka ha na ọmụmụ ihe dị ugbu a dị n'otu site na akụkọ banyere mmụba ọkụ ọkụ gburugburu otu PND [32], [33]. Ọmụmụ ihe ọmụmụ ugbu a atụleghị ọkwa basal extracellular ma ọ ga-ekwe omume na mmụba ọkụ ọkụ na-ebute mmụba basal na-enweghị ọnụ ọgụgụ ọ bụla na ntọhapụ nke potassium kpatara. Ọzọkwa, otu n'ime ọmụmụ ihe na-egosi ọkwa nke extracellular nke potassium kpatara na nucleus na-agbakọta ọnụ na gburugburu PND 42. [25] dị iche na data sitere na dorsal striatum, site na Stamford (1989) na ọmụmụ ihe ugbu a, nke na-egosi ọdịiche mpaghara.

Ihe nleba anya, T80, egosighi ọdịiche ọ bụla n'etiti afọ dị na ọmụmụ ihe ugbu a, ebe Stamford (1989) chọpụtara na ọnụ ọgụgụ nke elu dị elu na oke oke. Nke a nwere ike ịbụ n'ihi ọdịiche dị n'etiti usoro ihe eji eme ihe; T80 gụnyere ma akụkụ ahịrị na akụkụ curvilinear nke usoro ahụ, ebe Stamford ji akụkụ ahịrị ahịrị nke usoro ahụ. [34]. Ntụle e nwetara n'ime ọmụmụ ihe a bụ naanị otu ụzọ n'ụzọ iri nke nleba anya na ọmụmụ gara aga na V_max ya mere e kwesịghị iru. Iji akụkụ ahịrị nke ọnụ ụzọ elu iji gbakọọ ọnụego nnabata n'okpuru ọnọdụ ndị a ga-emepụta naanị ọnụego nnabata dabere na njupụta. [35]. A họọrọ T80 n'ihi na ọ na-eburu n'uche akụkụ curvilinear nke usoro ahụ, ebe ntinye dopamine dị ala ma na-enwe mmetụta nke ọma na ndị na-egbochi dopamine. [35], [36]. Dị ka o kwesịrị ịdị, T80 na-adaberekwa na njupụta, ma dị ka a pụrụ ịhụ n'ọmụmụ ihe a, ọdịiche dị na njupụta anaghị ebute ọdịiche dị na T80 ozugbo, na-atụ aro na oke nke ntinye na ntọhapụ na-atụgharị gaa n'inweta na ụmụ anụmanụ. Ịkwado nchoputa ugbu a bụ ọmụmụ nke jiri microdialysis quantitative ma chọpụta na ọ dịghị ihe dị iche na nkebi nke mmịpụta, ihe na-apụtaghị ìhè nke ọnụ ọgụgụ nnabata, na nucleus accumbens nke oke na PND 35, 45 na 60. [26].

Ntọhapụ nke potassium ka ukwuu n'oge ntozu nwere ike ịbụ n'ihi nnukwu ọdọ mmiri dopamine a na-ewepụta [12] na ọtụtụ ihe nwere ike itinye aka, dị ka ọdịiche dabere afọ na njikọ dopamine site na tyrosine hydroxylase. [29], [37], Vesicular monoamine transporter-2 (VMAT-2) nwere vesicles [38], na kinetics nke VMAT-2 [39], yana D2 nnata kwachaa [28] na arụ ọrụ [40]. Ihe ndị a nwekwara ike inye aka kọwapụta mmụba dị ukwuu a na-ahụ mgbe amphetamine gasịrị na ụmụ anụmanụ na-eto eto. Ọzọ, data dị ugbu a kwekọrọ na data na-egosi mmụba dị ukwuu na ntọhapụ dopamine na-eto eto ma e jiri ya tụnyere anụmanụ toro eto na nzaghachi nomifensine. [12] na-egosi na oke oke ndị na-eto eto nwere ọdọ mmiri nchekwa ka ukwuu, nke enwere ike ịwepụta ya na mkpali site na ihe ndị na-akpa ike. A na-akwado nke a site na data na-egosi mmụba dị ukwuu na dopamine extracellular kpaliri mgbe amphetamine na ụmụ anụmanụ na-eto eto [22]. Otú ọ dị, enwere ọmụmụ microdialysis na-egosi ọkwa dopamine dị ala mgbe amphetamine na-eto eto ma e jiri ya tụnyere ndị okenye. [30], [37], nke na-egosikwa ọzọ na ohere nke mmụba na ntọhapụ na-akpali akpali apụtaghị na ọ̀tụ̀tụ̀ dị n'ọkwa extracellular pụtara nakwa na usoro dị iche iche pụrụ itinye ozi na-emeju ihe.

Enweghị mmetụta dabere afọ na T80 mgbe achọpụtara amphetamine, nke na-egosi na amphetamine na-arụ ọrụ yiri nke ahụ na nnabata dopamine na afọ niile. Nke a na-akwado ọzọ site na nsonaazụ sitere na Stamford (1989), na-egosi enweghị ọdịiche dị na ogo mgbochi nnabata mgbe nomifensine dị n'etiti ndị ọgbọ. Enwekwara ọmụmụ ihe na-atụ aro na ndịiche metụtara afọ na nhazi ihe na-ebugharị dopamine na ọrụ metụtara ebe a na-ejikọta cocaine na onye na-ebu ya, ma ọ bụghị ebe amphetamine na-ejikọta ya. [22] nke nwere ike igosi na mmetụta amphetamine dabere na afọ anaghị adị. Otú ọ dị, e nwere omume na-eme ka mmekọrịta dị n'etiti oge, afọ na ọgwụgwọ, na-atụ aro na ha zaghachiri n'ụzọ dị iche n'oge amphetamine dabere na afọ. Ọmụmụ ihe ndị ọzọ na-enyocha nnabata ahụ site n'itinye dopamine exogenous nwekwara ike inye aka kewapụ njupụta na-adabere na njupụta site na ọrụ ụgbọ njem. [41]-[43]. Ọmụmụ banyere oke na-amụ anya ga-adịkwa mkpa, dịka a na-eme ọmụmụ ihe ugbu a n'ime anụmanụ ndị na-egbu egbu. Nkụnwụ ahụ e ji mee ihe bụ barbiturate thiobutabarbital (Inactin), ezigbo modulator allosteric modulator nke gamma-aminobutyric acid (GABA) A ndị na-anabata ya, nke na-emepụta nhụsianya ogologo ma kwụsie ike na oke. [44]. GABA nwere ike inwe mmetụta dị iche iche dabere na afọ na akụkọ ihe mere eme mmanya [45] ya mere, anesthesia nwere ike imekọrịta afọ ma ọ bụ ọgwụgwọ ma mepụta mmetụta na-agbagwoju anya. Agbanyeghị, pentobarbital, barbiturate ọzọ, egosila na ọ nwere mmetụta dị nta na ọkwa dopamine na striatum. [46]. Ọzọkwa, n'ime ọmụmụ ihe ugbu a, a kpaliri ntọhapụ site na iji potassium chloride ma ọ bụghị ịdabere na ihe omume mberede, nke kwesịrị ibelata mkpa ụda GABAergic dị na ntọhapụ. Banyere nnabata dopamine enwere akụkọ na barbiturates nwere ike imetụta nnabata dopamine kpọmkwem [47], mana ma enwere ike inwe mmekọrịta na afọ ma ọ bụ ọgwụgwọ amabeghị.

Ịṅụ mmanya na-aba n'anya n'oge ntorobịa afọ ofufo

Ịṅụ mmanya na-aba n'anya nke ndị nọ n'afọ iri na ụma ruo izu isii butere njupụta ntụaka dị ala ma e jiri ya tụnyere njikwa ịṅụ mmiri. Ngosipụta ndị ahụ yiri nke a na-ahụ na oke ndị na-eto eto. Ebe ọ bụ na a na-ahụ mmetụta ndị ahụ na njupụta ma ọ bụghị iwepụta oge, ọ ga-ekwe omume na mmanya na-emetụta ihe ndị na-achịkwa ọdọ mmiri nke dopamine karịa onye na-ebugharị dopamine na enwere data na-akwado nkwado na-enweghị mmetụta mgbe mmanya na-eto eto gasịrị. [14]. Enwekwara data microdialysis nke na-egosi mmụba nke dopamine extracellular ka ọ kpughesịrị n'afọ ntorobịa na intraperitoneal injections nke mmanya. [14], [27], [48], na nke a na-emegiderịta onwe ya na nchoputa ugbu a nke mbelata dopamine releasable. Dị ka e kwuru na mbụ, ụba ọkụ ọkụ nwere ike ịbụ ụzọ isi mee ka data microdialysis na data dị ugbu a dị n'otu, ma ọ dịghị ọmụmụ ihe iji kwado nke a. Ọzọkwa, enwere ọmụmụ ihe na-egosi na ụdị ikpughe mmanya, ya bụ nke afọ ofufo ma ọ bụ mmanye, nwere ike inwe mmetụta dị iche iche na neurobiology. [49].

Mgbe a na-agwọ ya na amphetamine, ọ nweghị nnukwu ọdịiche dị n'etiti mmanya na-aba n'anya na ndị na-aṅụ mmiri na amplitudes ma ọ bụ T80. Otú ọ dị, e nwere ihe a na-emekarị n'ebe mmetụta na amplitudes, n'ihi mmụba nke ndị na-aṅụ mmanya na-aba n'anya gosipụtara. Enwekwara mgbanwe dị iche iche na nzaghachi nke amphetamine na ìgwè ndị na-aṅụ mmanya na-aba n'anya, nke nwere ike ịbụ n'ihi mgbanwe nke ịṅụ mmanya na-aba n'anya, ọ bụ ezie na mgbanwe a adịghị ejikọta na nzaghachi (data egosighi). Nke a na-arụkwa aka na njedebe na ọmụmụ ihe a, ya bụ na a naghị atụle mmanya na-aba n'anya n'ọbara. Ọmụmụ ihe ahụ dabere na ịnweta enweghị nsogbu maka awa 24 yana maka ọkwa mmanya na-aba n'anya ọbara iji tụọ ohere ọ ga-abụrịrị na ọ ga-ejedebe na nrụgide dị na nlele ọbara ga-etinye aka na-akpaghasị usoro oriri nke anụmanụ. Ya mere, mmekọrịta dị n'etiti nzaghachi na ọkwa mmanya mmanya n'ọbara onye ọ bụla enweghị ike iwepụ. Otú ọ dị, data oriri na-egosi na ọmụmụ ihe a yiri ọmụmụ ihe ndị ọzọ, na-egosi mmetụta neurobiological nke mmanya na-aba n'anya, na-eji oke Wistar na afọ ndị yiri ya ma ọ bụ ihe oriri.[50]-[52]. Nke a na-egosi na ọ bụghị naanị ndị mmadụ na-enwekarị nnukwu oriri, kamakwa ndị na-aṅụbiga mmanya ókè site na mpaghara obe nke ọha mmadụ, na-enwe mgbanwe dị ize ndụ na neurobiology mgbe ịṅụ mmanya na-aba n'anya na-eto eto.

Enweghị ọdịiche dị na oge iweghachite mgbe amphetamine na-atụ aro na mmanya na-eto eto enweghị mmetụta na ọrụ ndị na-ebugharị dopamine na nzaghachi amphetamine, mana ọ ga-eritekwa uru na nyocha site na ntinye nke dopamine exogenous. [41]-[43].

Ọzọkwa, e mere ihe abụọ na-adọrọ mmasị. Nke mbu, nkwuwa okwu amplitudes mgbe ịṅụ mmanya na-aba n'anya yiri nke a na-ahụ na ụmụ anụmanụ na mmalite nke oge ịṅụ mmanya na-aba n'anya, ya bụ PND 28. Nke abuo, nha nke mmụba nke amplitudes mgbe amphetamine na anụ ndị na-aṅụ mmanya dị ka oge ikpeazụ. oke na-eto eto, ya bụ PND 42. Ma nchoputa ndị a metụtara mgbanwe mmepe nke ọdọ mmiri a na-ahapụ ya na ọdọ mmiri nchekwa dopamine na neurons ka ga-akọwapụta ya. Ọmụmụ ihe dị ugbu a agụnyeghị otu oke ndị na-aṅụ mmanya na-aba n'anya nke mere na enweghi ike ịchọta nkwubi okwu banyere ohere nke mmetụta afọ ole na ole. Otú ọ dị, e nwere ike ịhụ ihe ngosi nke mmetụta afọ ndụ na esemokwu dị n'etiti ọmụmụ banyere oke mmanya na-aba n'anya na-eto eto nke na-egosi nnabata dopamine na-adịghị emetụta. [14] na ọmụmụ banyere oke mmanya na-ekpughere oke na enwe nke na-egosi mmụba dị ukwuu, mana enweghị mmetụta na oke oke dopamine. [53], [54]. Maka ọmụmụ ihe n'ọdịnihu, ọ ga-enwe mmasị dị ukwuu iji nyochaa ikpughe mmanya na usoro n'azụ mmetụta ya na afọ dị iche iche. Nnyocha ndị ọzọ n'ime ihe ndị dị ka tyrosine hydroxylase, dopamine receptor density and function, na vesicular monoamine transporter nwere ike inye aka mee ka ìhè dị na mmetụta mmanya nwere ike ime afọ na ọdọ mmiri a na-ahapụ na ebe nchekwa nke dopamine. Dị ka anyị maara, enyochabeghị ihe ndị a mgbe mmanya na-eto eto gasịrị.

mmechi

Ihe omuma a na-egosi mmụba nke nta nke nta nke dopamine na-ejupụta na afọ, na-akwado ọmụmụ ihe gara aga na-atụ aro na ọdọ mmiri nke dopamine na-ewepụta na-abawanye na afọ. N'ụzọ dị iche, a na-ahụ mbelata nke nta nke nta nke oke njupụta nke afọ na nzaghachi nke amphetamine, na-akwado nnukwu nchekwa nchekwa nke dopamine n'ime ụmụ anụmanụ na-eto eto, na-eme ka ha nwekwuo mmetụta maka ọgwụ ndị na-ewepụta dopamine. Ịṅụ mmanya na-aba n'anya na-eto eto mere ka mmiri jubiga ókè karịa na nchịkwa ịṅụ mmiri., Na-egosi na mmanya na-emetụta ọdọ mmiri nke dopamine na nke a nwere ike inwe mmetụta maka adịghị ike na ịṅụ ọgwụ ọjọọ na nchọpụta ọrịa uche ndị ọzọ metụtara usoro dopamine na dorsal striatum.

Nkweta

Ndị ode akwụkwọ chọrọ ikele Oriakụ Marita Berg maka enyemaka aka ọrụ yana Dr. Martin Lundblad maka mkparịta ụka usoro.

Onye nyere onyinye

Chepụtara ma chepụta nnwale ndị a: SP IN. Emere nnwale ndị a: SP. Nyochaa data: SP IN. Dee akwụkwọ a: SP.