IZIMVO: Uphononongo lokuqala olubonisa ukuba ukusetyenziswa kweziyobisi kubangela ukuhla kwe-dopamine (D2) receptors. Kubalulekile kuba abakhobokileyo banenani eliphantsi lezo zamkeli, ezinokuthi zibe negalelo ekubeni likhoboka. Kwakhona kubonisa ukuba i-receptors inokubuyela emva, kodwa izinga liguquguquka kakhulu kwaye alihambelani nesiseko se-D2 receptors.
Ukuxhatshazwa kweCocaine kunye namaNqanaba oMmkeli: I-PET Imaging iqinisekisa ikhonkco
14 Jul 2006
Besebenzisa i-positron emission tomography (PET), abaphandi baye baseka unxibelelwano oluqinileyo phakathi kwendlela ethile yekhemistri yobuchopho kunye notyekelo lomntu lokusebenzisa kakubi icocaine kwaye mhlawumbi abe likhoboka, ecebisa iindlela zonyango ezinokubakho.
Uphando, kwizilwanyana, lubonisa unxibelelwano olubalulekileyo phakathi kwenani lee-receptors kwinxalenye yengqondo ye-neurotransmitter dopamine - elinganiswe ngaphambi kokuba kuqale ukusetyenziswa kwe-cocaine- kunye nenqanaba apho isilwanyana siya kuthi kamva sizisebenzise ngokwaso ichiza. Uphando lwenziwa kwiinkawu ze-rhesus, ezithathwa njengemodeli ebalaseleyo yabasebenzisi beziyobisi zabantu.
Ngokubanzi esezantsi inani lokuqala le-dopamine receptors, liphezulu izinga lokusetyenziswa kwe-cocaine, abaphandi bafumene. Uphando lukhokelwa nguMichael A. Nader, Ph.D., uprofesa we-physiology kunye ne-pharmacology kwi-Wake Forest University School of Medicine.
Kwakusele kusaziwa ukuba abaxhaphazi be-cocaine babenamanqanaba asezantsi e-dopamine receptor eyaziwa ngokuba yi-D2, kuzo zombini izifundo zabantu kunye nezilwanyana, xa kuthelekiswa nabangabasebenzisi. Kodwa kwakungaziwa ukuba ngaba leyo yayiyimpawu eyayikho ngaphambili eyayibeka abantu phambili ekusebenziseni kakubi i-cocaine okanye sisiphumo sokusetyenziswa kwe-cocaine.
"Okufunyenweyo ngoku kwiinkawu kubonisa ukuba zombini ezi zinto zinokuba yinyani,"
UNader kunye noogxa babhala kuphononongo olupapashwe kwi-intanethi kule veki kwijenali yeNdalo Neuroscience. "Izinto ezifunyenweyo ngoku zikwacebisa ukuba abantu abasesichengeni ngakumbi banokuqhubeka nokusebenzisa i-cocaine ngenxa yokuncipha kwe-cocaine kumanqanaba e-D2 receptor."
Esi yayisisifundo sokuqala sokulinganisa amanqanaba esiseko e-D2 yezilwanyana ezingazange zisebenzise i-cocaine kwaye zithelekise loo manqanaba kwiinguqu kwi-D2 receptors emva kokuba izilwanyana ziqalise ukusebenzisa. Olu hlobo lokuthelekisa alunakwenzeka kwizifundo zabantu, kunye nophando lwangaphambili lwenkawu, imichiza yobuchopho yezilwanyana ezivezwe kwi-cocaine yathelekiswa kuphela "nolawulo" olungasebenzisi.
Uphando luye lwabonisa ukuba ukuqala ukusebenzisa I-cocaine ibangele amanqanaba e-D2 ukuba ehle kakhulu kwaye ukuqhubeka nokusebenzisa ichiza kugcine amanqanaba e-D2 ngaphantsi kwesiseko.
Ngokubanzi, ezi zinto zifunyanisiweyo zibonelela ngobungqina obungathandabuzekiyo bendima ye- [dopamine] i-D2 receptors ekusebenziseni kakubi i-cocaine kwaye icebisa ukuba unyango olujolise ekunyuseni amanqanaba e-D2 receptors lunokuba nesithembiso sokunciphisa ukongezwa kweziyobisi,” abaphandi babhala.
Uphononongo lucebise ukuba ukwanda kwe-D2 receptors kunokwenziwa "kwi-pharmacologically" okanye ngokuphucula iimeko zokusingqongileyo, ezifana nokunciphisa uxinzelelo. Kodwa, uphononongo luthi, "okwangoku alukho unyango olusebenzayo lwe-cocaine, kwaye ukuqonda kwabalamli bebhayoloji kunye nokusingqongileyo ukuba sesichengeni sokusetyenziswa kakubi kwe-cocaine kuhlala kunzima."
I-Dopamine, njengezinye ii-neurotransmitters, ihamba phakathi kweeseli zemithambo-luvo engqondweni ukuze idlulise “imiyalezo” ethile. Ikhutshwa yiseli yemithambo-luvo enye ize ithathwe zii-receptors kwiseli yemithambo-luvo elandelayo, ezinye zazo ziyi-D2. I-dopamine engasetyenziswanga iqokelelwa "kwizithuthi" ezibuyisela kwiseli yokuthumela.
I-Cocaine isebenza ngokungena kwi-transporter, ivimbela "i-reuptake" ye-dopamine kwaye ishiye ngaphezulu kwayo kwindawo phakathi kweeseli. Kucingelwa ukuba oku kugcwala kwe-dopamine kunika umsebenzisi i-cocaine "phezulu."
Kodwa le dopamine igcwele kakhulu iphinda igqithise i-D2 receptors kwiiseli ezifumanayo, kwaye ezo seli ekugqibeleni zisabela ngokunciphisa inani le-D2 receptors. Abaphandi beziyobisi baqikelela ukuba lutshintsho oludala umnqweno wecocaine: nje ukuba inqanaba le-receptor lehlile, i-dopamine eninzi iyafuneka ukuze umsebenzisi azive "eqhelekileyo."
Njengokusetyenziswa kwe-cocaine, uxinzelelo lunokunyusa amanqanaba e-dopamine kwaye ngokucacileyo lubangele ukuncipha kwe-D2 receptors. Uphando lwakwangoko olwenziwe liqela likaNader eWake Forest lubonise unxibelelwano phakathi koxinzelelo kunye notyekelo lokusebenzisa kakubi icocaine.
Uphononongo lwangoku luphinde lwabona umahluko kwixesha elithathiweyo ukuba i-D2 receptors ibuyele kumanqanaba aqhelekileyo nje ukuba ukusetyenziswa kwe-cocaine kuphelile. Iinkawu ezisetyenziselwa kuphela iveki enye zineepesenti ezili-15 kuphela zokunciphisa i-D2 receptors kwaye zachacha ngokupheleleyo kwiiveki ezintathu.
Kodwa iinkawu ezazisetyenziselwa unyaka zinciphisa ipesenti ezingama-21 kwi-D2 receptors. Ezintathu kwezo nkawu zachacha kwisithuba seenyanga ezintathu, kodwa ezimbini kwezo nkawu zazingekabuyeli kumanqanaba azo e-D2 asisiseko emva konyaka omnye wokuziyeka.
Ukungabikho kokubuyisela kwakungahambelani namanqanaba okuqala e-D2. Uphononongo lucebisa ukuba "ezinye izinto, mhlawumbi ezibandakanya ezinye iinkqubo ze-neurotransmitter, zilamla ukubuyiswa komsebenzi we-D2 receptor."
ISIFUNDO: Umfanekiso we-PET we-dopamine D2 receptors ngexesha lokuzilawula okungapheliyo kwe-cocaine kwiinkawu.
Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL,
Buchheimer N, Ehrenkaufer R, Mach RH.
Nat Neurosci. 2006 Aug;9(8):1050-6. Epub 2006 Jul 9.
ISebe lePhysiology kunye ne-Pharmacology, i-Wake Forest University School of Medicine, yezoNyango
Centre Boulevard, Winston-Salem, North Carolina 27157, USA. [imeyile ikhuselwe]
I-Dopamine neurotransmission inxulunyaniswa nokuba sesichengeni esiphezulu sokusetyenziswa kakubi kwe-cocaine. I-Positron emission tomography yasetyenziswa kwii-rhesus macaques ezili-12 ukufumanisa ukuba ngaba ukufumaneka kwe-dopamine D2 receptor yayanyaniswa nesantya sokuqiniswa kwe-cocaine, kunye nokufunda utshintsho kumsebenzi wengqondo ye-dopaminergic ngexesha lokugcinwa kunye nokuyeka i-cocaine. Isiseko sokufumaneka kwe-receptor ye-D2 yayinxulunyaniswa kakubi namazinga okuzilawula kwe-cocaine. Ukufumaneka kwe-receptor ye-D2 kwehle nge-15-20% ngaphakathi kweveki ye-1 yokuqalisa ukuzilawula kwaye yahlala iyancipha malunga ne-20% ngexesha le-1 ngonyaka wokuvezwa. Ukunciphisa ixesha elide ekufumanekeni kwe-D2 receptor kwabonwa, kunye nokuncipha okuqhubekayo ukuya kwi-1 unyaka wokuziyeka kwezinye iinkawu. Ezi datha zibonelela ngobungqina be-predisposition yokuzilawula ngokwakho i-cocaine esekwe kubukho be-D2 receptor, kwaye ibonisa ukuba inkqubo ye-dopamine yobuchopho iphendula ngokukhawuleza emva kokuvezwa kwe-cocaine. Ukwahluka komntu ngamnye kwinqanaba lokubuyisela umsebenzi we-D2 receptor ngexesha lokuziyeka kwaphawulwa.
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