{"id":{"repo_id":"helsinki","oai_identifier":"oai:helda.helsinki.fi:10138/17172"},"canonical_url":"https://search.dev.ndltd.org/etd/helsinki/oai:helda.helsinki.fi:10138/17172","repository":{"repo_id":"helsinki","name":"University of Helsinki","base_url":"https://helda.helsinki.fi/server/oai/request"},"display":{"title":"Morfiinin vaikutukset ehdollistetussa paikkahakuisuuskokeessa AMPA-tyypin glutamaattireseptorin GluA1-alayksikön poistogeenisillä hiirillä","abstract":"Glutamate is the principal excitatory neurotransmitter in the central nervous system. Glutamatergic neurotransmission plays a central role in the development and maintenance of drug addiction. Glutamate interacts with other neurotransmitters such as dopamine in the actions concerning addiction. During the development of drug addiction, plastic changes in the neuronal connections related to memory and learning occur for example in the amount of synapses and in the efficacy of their action. Glutamatergic AMPA receptor and especially its GluA1 subunit are thought to be included in the neurobiological mechanisms related to drug addiction. Compulsive drug craving and relapses to drug use after a period of abstinence are central problems among people suffering drug addiction. Conditioned place preference is a technique that is used to study motivational properties of drugs in experimental animals. The aim of this master's thesis was to examine the importance of glutamatergic AMPA receptor GluA1 subunit in the morphine-induced place preference and in its extinction and reinstatement behaviour. Locomotor activity of mice was studied during all the phases of experiment. Glutamatergic AMPA receptor GluA1 subunit-deficient (GluA1-/-) and their control (wildtype) mice, based on C57BL/6J mouse strain, were used in the experiments. During the conditioning phase, the mice were trained to associate the effects of morphine (20 mg/kg) with a specific environment. After conditioning, the extinction with morphine paired conditioning environment was assessed by giving saline (0,9 % NaCl solution) to mice. The extinction phase was followed by reinstatement test, in which mice were given morphine (20 mg/kg). The seeking of animals with morphine paired conditioning environment described drug-seeking during different phases of experiment. GluA1-/- mice were more hyperactive when placed in the testing environment compared to the wildtype mice. However, the morphine-induced locomotor activity did not differ between genotypes. Locomotor activity of both genotypes was sensitized equally in consequence of repeated morphine exposures. Morphine induced place preference in both genotypes. Furthermore, the extinction of morphine place preference happened in both genotypes. However, the results of reinstatement test differed partly between genotypes. The place preference was reinstated by morphine in wildtype mice, but not in GluA1-/- mice, when using repeated testing extinction method. Instead of place preference, wildtype mice exhibited place aversion, when extinction method was saline conditioning. As a result of these experiments, extinction method can have an impact on the results of reinstatement test and conclusions cannot be done on the importance of GluA1 subunit in morphine reinstatement. In conclusion, the results of place preference experiments support the conception that GluA1 subunit is not significant in morphine conditioning. However, based on these experiments, GluA1 subunit is not important in morphine extinction, as one might assume on the basis of literature. GluA1 subunit may have an importance in morphine reinstatement, although the results of reinstatement test were partly contradictory.","abstract_html":"Glutamate is the principal excitatory neurotransmitter in the central nervous system. Glutamatergic neurotransmission plays a central role in the development and maintenance of drug addiction. Glutamate interacts with other neurotransmitters such as dopamine in the actions concerning addiction. During the development of drug addiction, plastic changes in the neuronal connections related to memory and learning occur for example in the amount of synapses and in the efficacy of their action. Glutamatergic AMPA receptor and especially its GluA1 subunit are thought to be included in the neurobiological mechanisms related to drug addiction. Compulsive drug craving and relapses to drug use after a period of abstinence are central problems among people suffering drug addiction. Conditioned place preference is a technique that is used to study motivational properties of drugs in experimental animals. The aim of this master's thesis was to examine the importance of glutamatergic AMPA receptor GluA1 subunit in the morphine-induced place preference and in its extinction and reinstatement behaviour. Locomotor activity of mice was studied during all the phases of experiment. Glutamatergic AMPA receptor GluA1 subunit-deficient (GluA1-/-) and their control (wildtype) mice, based on C57BL/6J mouse strain, were used in the experiments. During the conditioning phase, the mice were trained to associate the effects of morphine (20 mg/kg) with a specific environment. After conditioning, the extinction with morphine paired conditioning environment was assessed by giving saline (0,9 % NaCl solution) to mice. The extinction phase was followed by reinstatement test, in which mice were given morphine (20 mg/kg). The seeking of animals with morphine paired conditioning environment described drug-seeking during different phases of experiment. GluA1-/- mice were more hyperactive when placed in the testing environment compared to the wildtype mice. However, the morphine-induced locomotor activity did not differ between genotypes. Locomotor activity of both genotypes was sensitized equally in consequence of repeated morphine exposures. Morphine induced place preference in both genotypes. Furthermore, the extinction of morphine place preference happened in both genotypes. However, the results of reinstatement test differed partly between genotypes. The place preference was reinstated by morphine in wildtype mice, but not in GluA1-/- mice, when using repeated testing extinction method. Instead of place preference, wildtype mice exhibited place aversion, when extinction method was saline conditioning. As a result of these experiments, extinction method can have an impact on the results of reinstatement test and conclusions cannot be done on the importance of GluA1 subunit in morphine reinstatement. In conclusion, the results of place preference experiments support the conception that GluA1 subunit is not significant in morphine conditioning. However, based on these experiments, GluA1 subunit is not important in morphine extinction, as one might assume on the basis of literature. GluA1 subunit may have an importance in morphine reinstatement, although the results of reinstatement test were partly contradictory.","abstract_has_math":false,"creators":["Ojala, Katja"],"institution":"Helsingfors universitet","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Helsingin yliopisto, Farmasian tiedekunta","University of Helsinki, Faculty of Pharmacy","Helsingfors universitet, Farmaceutiska fakulteten"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010","date_published":"2010","updated_at":"2026-07-27T19:56:27Z","subjects":["AMPA","addiction","glutamate","knockout mouse","conditioned place preference","locomotor activity","morphine","riippuvuus","glutamaatti","poistogeeninen hiiri","ehdollistettu paikkahakuisuus","morfiini","lokomotorinen aktiivisuus"],"languages":["fin"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["URN:NBN:fi-fe20180115195"],"render_values":[{"text":"URN:NBN:fi-fe20180115195","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10138/17172","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Helsingin yliopisto, Farmasian tiedekunta","University of Helsinki, Faculty of Pharmacy","Helsingfors universitet, Farmaceutiska fakulteten"]},{"key":"dc:creator","label":"Author","values":["Ojala, Katja"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2010"]},{"key":"dc:publisher","label":"Institution","values":["Helsingfors universitet","University of Helsinki","Helsingin yliopisto"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["AMPA","addiction","glutamate","knockout mouse","conditioned place preference","locomotor activity","morphine","riippuvuus","glutamaatti","poistogeeninen hiiri","ehdollistettu paikkahakuisuus","morfiini","lokomotorinen aktiivisuus"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["fin"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["URN:NBN:fi-fe20180115195","http://hdl.handle.net/10138/17172"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Glutamate is the principal excitatory neurotransmitter in the central nervous system. Glutamatergic neurotransmission plays a central role in the development and maintenance of drug addiction. Glutamate interacts with other neurotransmitters such as dopamine in the actions concerning addiction. During the development of drug addiction, plastic changes in the neuronal connections related to memory and learning occur for example in the amount of synapses and in the efficacy of their action. Glutamatergic AMPA receptor and especially its GluA1 subunit are thought to be included in the neurobiological mechanisms related to drug addiction. Compulsive drug craving and relapses to drug use after a period of abstinence are central problems among people suffering drug addiction. Conditioned place preference is a technique that is used to study motivational properties of drugs in experimental animals. The aim of this master's thesis was to examine the importance of glutamatergic AMPA receptor GluA1 subunit in the morphine-induced place preference and in its extinction and reinstatement behaviour. Locomotor activity of mice was studied during all the phases of experiment. Glutamatergic AMPA receptor GluA1 subunit-deficient (GluA1-/-) and their control (wildtype) mice, based on C57BL/6J mouse strain, were used in the experiments. During the conditioning phase, the mice were trained to associate the effects of morphine (20 mg/kg) with a specific environment. After conditioning, the extinction with morphine paired conditioning environment was assessed by giving saline (0,9 % NaCl solution) to mice. The extinction phase was followed by reinstatement test, in which mice were given morphine (20 mg/kg). The seeking of animals with morphine paired conditioning environment described drug-seeking during different phases of experiment. GluA1-/- mice were more hyperactive when placed in the testing environment compared to the wildtype mice. However, the morphine-induced locomotor activity did not differ between genotypes. Locomotor activity of both genotypes was sensitized equally in consequence of repeated morphine exposures. Morphine induced place preference in both genotypes. Furthermore, the extinction of morphine place preference happened in both genotypes. However, the results of reinstatement test differed partly between genotypes. The place preference was reinstated by morphine in wildtype mice, but not in GluA1-/- mice, when using repeated testing extinction method. Instead of place preference, wildtype mice exhibited place aversion, when extinction method was saline conditioning. As a result of these experiments, extinction method can have an impact on the results of reinstatement test and conclusions cannot be done on the importance of GluA1 subunit in morphine reinstatement. In conclusion, the results of place preference experiments support the conception that GluA1 subunit is not significant in morphine conditioning. However, based on these experiments, GluA1 subunit is not important in morphine extinction, as one might assume on the basis of literature. GluA1 subunit may have an importance in morphine reinstatement, although the results of reinstatement test were partly contradictory.","Glutamaatti on keskushermoston pääasiallinen eksitatorinen eli toimintaa kiihdyttävä välittäjäaine. Glutamatergisen hermovälityksen merkitys päihderiippuvuuden kehittymisessä ja ylläpidossa on keskeinen. Glutamaatti on vuorovaikutuksessa muiden välittäjäaineiden kuten dopamiinin kanssa riippuvuuteen liittyvissä tapahtumissa. Päihderiippuvuuden kehittyessä tapahtuu muistiin ja oppimiseen liittyviä hermosoluyhteyksien plastisia muutoksia esimerkiksi synapsien määrässä ja niiden toiminnan tehokkuudessa. Glutamatergisen AMPA-reseptorin ja erityisesti sen GluA1- alayksikön uskotaan sisältyvän riippuvuuden taustalla oleviin neurobiologisiin mekanismeihin. Päihderiippuvuudesta kärsivillä ihmisillä on keskeisinä ongelmina pakonomainen halu käyttää päihdettä ja raittiiden kausien jälkeen tapahtuvat retkahtamiset päihteisiin. Päihteiden aiheuttamaa palkitsevuutta voidaan mallintaa ehdollistetun paikkahakuisuusmenetelmän avulla. Erikoistyön tavoitteena oli selvittää glutamatergisen AMPA-reseptorin GluA1-alayksikön merkitystä hiirillä morfiinin paikkahakuisuudessa ja sen sammumisessa sekä retkahduskäyttäytymisessä. Hiirien lokomotorista aktiivisuutta tutkittiin kaikkien koevaiheiden aikana. Koe-eläiminä käytettiin C57BL/6J hiirikannan pohjalta kehiteltyjä glutamatergisen AMPA-reseptorin suhteen GluA1 villityypin ja GluA1 poistogeenisiä (GluA1-/-) hiiriä. Ehdollistamisvaiheessa hiiret opetettiin yhdistämään morfiinin (20 mg/kg) vaikutukset tiettyyn ympäristöön. Ehdollistamisen jälkeen arvioitiin ehdollistumisen sammumista eli ekstinktiota morfiiniin liitettyyn ehdollistamisympäristöön antamalla hiirille saliinia (0,9 % NaCl-liuos). Ekstinktiovaihetta seurasi retkahdustesti, jonka yhteydessä hiirille annettiin morfiinia (20 mg/kg). Eläinten hakeutuminen morfiiniin liitettyyn ehdollistamisympäristöön kuvasi päihdehakuisuutta eri koevaiheiden aikana. GluA1-/- hiiret olivat hyperaktiivisempia koeympäristössä villityypin hiiriin verrattuna. Morfiinin indusoima liikkuminen ei kuitenkaan eronnut genotyyppien välillä, vaan molempien genotyyppien lokomotorinen aktiivisuus herkistyi yhtä lailla toistuvien morfiinialtistuksien seurauksena. Morfiini aiheutti myös paikkahakuisuutta molemmilla genotyypeillä. Morfiinin paikkahakuisuus sammui edelleen kummallakin genotyypillä. Retkahdustestin tulokset erosivat kuitenkin osittain genotyyppien välillä. Villityypin hiiret retkahtivat morfiiniin, kun käytettiin toistettujen testien ekstinktiomenetelmää, mutta GluA1-/- hiiret eivät. Villityypin hiirillä esiintyi paikkahakuisuuden sijaan paikka-aversiota retkahdustestissä, kun ekstinktiomenetelmänä oli saliinilla ehdollistaminen. Näiden kokeiden perusteella ekstinktiomenetelmällä saattaa olla vaikutusta retkahdustestin tuloksiin, eikä koetulosten perusteella voi tehdä johtopäätöksiä GluA1-alayksikön merkityksestä morfiiniin retkahtamisessa. Yhteenvetona voidaan todeta, että paikkaehdollistamiskokeiden tulokset tukevat käsitystä, minkä perusteella GluA1-alayksikkö ei ole merkittävä morfiiniin ehdollistumisessa. Koetulosten perusteella GluA1-alayksiköllä ei ole kuitenkaan merkitystä morfiinin ekstinktiossa, kuten kirjallisuuden perusteella voi olettaa. GluA1-alayksiköllä saattaa olla merkitystä morfiiniin retkahtamisessa, vaikka retkahdustestin tulokset olivat osittain ristiriitaisia."]},{"key":"dc:title","label":"Title","values":["Morfiinin vaikutukset ehdollistetussa paikkahakuisuuskokeessa AMPA-tyypin glutamaattireseptorin GluA1-alayksikön poistogeenisillä hiirillä"]}]}],"canonical_facts":{"dc:contributor":["Helsingin yliopisto, Farmasian tiedekunta","University of Helsinki, Faculty of Pharmacy","Helsingfors universitet, Farmaceutiska fakulteten"],"dc:creator":["Ojala, Katja"],"dc:date.issued":["2010"],"dc:description.abstract":["Glutamate is the principal excitatory neurotransmitter in the central nervous system. Glutamatergic neurotransmission plays a central role in the development and maintenance of drug addiction. Glutamate interacts with other neurotransmitters such as dopamine in the actions concerning addiction. During the development of drug addiction, plastic changes in the neuronal connections related to memory and learning occur for example in the amount of synapses and in the efficacy of their action. Glutamatergic AMPA receptor and especially its GluA1 subunit are thought to be included in the neurobiological mechanisms related to drug addiction. Compulsive drug craving and relapses to drug use after a period of abstinence are central problems among people suffering drug addiction. Conditioned place preference is a technique that is used to study motivational properties of drugs in experimental animals. The aim of this master's thesis was to examine the importance of glutamatergic AMPA receptor GluA1 subunit in the morphine-induced place preference and in its extinction and reinstatement behaviour. Locomotor activity of mice was studied during all the phases of experiment. Glutamatergic AMPA receptor GluA1 subunit-deficient (GluA1-/-) and their control (wildtype) mice, based on C57BL/6J mouse strain, were used in the experiments. During the conditioning phase, the mice were trained to associate the effects of morphine (20 mg/kg) with a specific environment. After conditioning, the extinction with morphine paired conditioning environment was assessed by giving saline (0,9 % NaCl solution) to mice. The extinction phase was followed by reinstatement test, in which mice were given morphine (20 mg/kg). The seeking of animals with morphine paired conditioning environment described drug-seeking during different phases of experiment. GluA1-/- mice were more hyperactive when placed in the testing environment compared to the wildtype mice. However, the morphine-induced locomotor activity did not differ between genotypes. Locomotor activity of both genotypes was sensitized equally in consequence of repeated morphine exposures. Morphine induced place preference in both genotypes. Furthermore, the extinction of morphine place preference happened in both genotypes. However, the results of reinstatement test differed partly between genotypes. The place preference was reinstated by morphine in wildtype mice, but not in GluA1-/- mice, when using repeated testing extinction method. Instead of place preference, wildtype mice exhibited place aversion, when extinction method was saline conditioning. As a result of these experiments, extinction method can have an impact on the results of reinstatement test and conclusions cannot be done on the importance of GluA1 subunit in morphine reinstatement. In conclusion, the results of place preference experiments support the conception that GluA1 subunit is not significant in morphine conditioning. However, based on these experiments, GluA1 subunit is not important in morphine extinction, as one might assume on the basis of literature. GluA1 subunit may have an importance in morphine reinstatement, although the results of reinstatement test were partly contradictory.","Glutamaatti on keskushermoston pääasiallinen eksitatorinen eli toimintaa kiihdyttävä välittäjäaine. Glutamatergisen hermovälityksen merkitys päihderiippuvuuden kehittymisessä ja ylläpidossa on keskeinen. Glutamaatti on vuorovaikutuksessa muiden välittäjäaineiden kuten dopamiinin kanssa riippuvuuteen liittyvissä tapahtumissa. Päihderiippuvuuden kehittyessä tapahtuu muistiin ja oppimiseen liittyviä hermosoluyhteyksien plastisia muutoksia esimerkiksi synapsien määrässä ja niiden toiminnan tehokkuudessa. Glutamatergisen AMPA-reseptorin ja erityisesti sen GluA1- alayksikön uskotaan sisältyvän riippuvuuden taustalla oleviin neurobiologisiin mekanismeihin. Päihderiippuvuudesta kärsivillä ihmisillä on keskeisinä ongelmina pakonomainen halu käyttää päihdettä ja raittiiden kausien jälkeen tapahtuvat retkahtamiset päihteisiin. Päihteiden aiheuttamaa palkitsevuutta voidaan mallintaa ehdollistetun paikkahakuisuusmenetelmän avulla. Erikoistyön tavoitteena oli selvittää glutamatergisen AMPA-reseptorin GluA1-alayksikön merkitystä hiirillä morfiinin paikkahakuisuudessa ja sen sammumisessa sekä retkahduskäyttäytymisessä. Hiirien lokomotorista aktiivisuutta tutkittiin kaikkien koevaiheiden aikana. Koe-eläiminä käytettiin C57BL/6J hiirikannan pohjalta kehiteltyjä glutamatergisen AMPA-reseptorin suhteen GluA1 villityypin ja GluA1 poistogeenisiä (GluA1-/-) hiiriä. Ehdollistamisvaiheessa hiiret opetettiin yhdistämään morfiinin (20 mg/kg) vaikutukset tiettyyn ympäristöön. Ehdollistamisen jälkeen arvioitiin ehdollistumisen sammumista eli ekstinktiota morfiiniin liitettyyn ehdollistamisympäristöön antamalla hiirille saliinia (0,9 % NaCl-liuos). Ekstinktiovaihetta seurasi retkahdustesti, jonka yhteydessä hiirille annettiin morfiinia (20 mg/kg). Eläinten hakeutuminen morfiiniin liitettyyn ehdollistamisympäristöön kuvasi päihdehakuisuutta eri koevaiheiden aikana. GluA1-/- hiiret olivat hyperaktiivisempia koeympäristössä villityypin hiiriin verrattuna. Morfiinin indusoima liikkuminen ei kuitenkaan eronnut genotyyppien välillä, vaan molempien genotyyppien lokomotorinen aktiivisuus herkistyi yhtä lailla toistuvien morfiinialtistuksien seurauksena. Morfiini aiheutti myös paikkahakuisuutta molemmilla genotyypeillä. Morfiinin paikkahakuisuus sammui edelleen kummallakin genotyypillä. Retkahdustestin tulokset erosivat kuitenkin osittain genotyyppien välillä. Villityypin hiiret retkahtivat morfiiniin, kun käytettiin toistettujen testien ekstinktiomenetelmää, mutta GluA1-/- hiiret eivät. Villityypin hiirillä esiintyi paikkahakuisuuden sijaan paikka-aversiota retkahdustestissä, kun ekstinktiomenetelmänä oli saliinilla ehdollistaminen. Näiden kokeiden perusteella ekstinktiomenetelmällä saattaa olla vaikutusta retkahdustestin tuloksiin, eikä koetulosten perusteella voi tehdä johtopäätöksiä GluA1-alayksikön merkityksestä morfiiniin retkahtamisessa. Yhteenvetona voidaan todeta, että paikkaehdollistamiskokeiden tulokset tukevat käsitystä, minkä perusteella GluA1-alayksikkö ei ole merkittävä morfiiniin ehdollistumisessa. Koetulosten perusteella GluA1-alayksiköllä ei ole kuitenkaan merkitystä morfiinin ekstinktiossa, kuten kirjallisuuden perusteella voi olettaa. GluA1-alayksiköllä saattaa olla merkitystä morfiiniin retkahtamisessa, vaikka retkahdustestin tulokset olivat osittain ristiriitaisia."],"dc:identifier.uri":["URN:NBN:fi-fe20180115195","http://hdl.handle.net/10138/17172"],"dc:language.iso":["fin"],"dc:publisher":["Helsingfors universitet","University of Helsinki","Helsingin yliopisto"],"dc:subject":["AMPA","addiction","glutamate","knockout mouse","conditioned place preference","locomotor activity","morphine","riippuvuus","glutamaatti","poistogeeninen hiiri","ehdollistettu paikkahakuisuus","morfiini","lokomotorinen aktiivisuus"],"dc:title":["Morfiinin vaikutukset ehdollistetussa paikkahakuisuuskokeessa AMPA-tyypin glutamaattireseptorin GluA1-alayksikön poistogeenisillä hiirillä"]},"updated_at":"2026-07-27T19:56:27Z"}