Från att du föds, genom hela din ungdomstid och fram till att du befinner dig i mitten av 20-årsåldern så utvecklas och mognar din hjärna. Under den här tiden är hjärnan även extra känslig för olika former av yttre påverkan. Två exempel på faktorer som kan ha negativ effekt på hjärnan är stress och expo-nering av droger. Om du växer upp i en otrygg och stressfylld miljö eller utsätts för upprepad exponering av droger i ung ålder så ökar exempelvis risken att du drabbas av en psykiatrisk sjukdom senare i livet.
Den här avhandlingen har undersökt hur två av hjärnans signalsubstanser, dopamin och endogena opioider (kroppsegna morfinliknande ämnen), på-verkas när en ung individ utsätts för stress eller upprepat intag av alkohol.
Dopamin och endogena opioider utgör en viktig del av hjärnans belönings-system och hjälper till att förmedla de positiva känslor som du upplever när du till exempel äter en god middag, har sex eller uppnår en framgång. Dessa positiva känslor kallas för naturlig belöning. Men det är inte bara vid naturlig belöning som aktiviteten av dopamin och endogena opioider ökar, även alla beroendeframkallande droger har den här egenskapen.
För att undersöka hur den unga hjärnan påverkas av droger eller stress an-vänds ofta djurmodeller. Anledningen är att dessa frågeställningar är svåra att besvara i människa på grund av etiska principer. I den här avhandlingen har därför djurmodeller använts för att simulera olika typer av negativa livs-händelser som förknippas med en otrygg uppväxtmiljö. I en av avhandling-ens studier stördes kontakten mellan mamman och ungarna genom tidsbe-gränsade separationer av nyfödda råttungar och i en annan av studierna pla-cerades unga råttor tidvis ensamma för att efterlikna en miljö med störd social kontakt. Alkohol gavs även till unga råttor för att undersöka hur alko-hol påverkar den unga hjärnan.
Resultaten från studierna visade bland annat att en otrygg uppväxtmiljö påverkade endogena opioider i dorsala striatum - en del av hjärnan som bland annat är kopplad till bildandet av vanor. En otrygg uppväxt förändrade även hur de endogena opioiderna svarade på alkoholintag i vuxen ålder. De endogena opioiderna påverkades även av en störd social miljö under ung-domstiden då minskade nivåer sågs i många av hjärnans olika regioner.
Kvarvarande förändringar i både endogena opioider och dopamin syntes efter att alkohol intagits under ungdomstiden. Intaget av alkohol i ung ålder hade ingen effekt på viljan att självadministrera amfetamin, däremot skiljde
sig dopaminaktiviteten åt i dorsala striatum efter en injektion av amfetamin i vuxen ålder.
Otrygghet, stress och alkohol formar med andra ord den unga hjärnan och förändrar dess belöningssystem. Detta kan, till viss del, förklara varför en otrygg uppväxtmiljö och upprepat intag av droger i ung ålder ökar risken för psykiatrisk sjukdom senare i livet.
Acknowledgment
Now this period of my life is finished, without my main supervisor Ingrid Nylander it would not have been possible. Thank you for believing in me!
To know that you have trust in what I do creates a stimulating environment to work in. Even if you have tons of work to do, you always try to find some time to help. I´m very happy to have had you as my main supervisor!
My co-supervisors. Anne-Lie Svensson, you are the gate-way to a PhD.
Without your fantastic supervision during SOFOSKO projects, many theses would not have been written. You are one of the most positive persons I know! Maria Ellgren, I have missed you a lot since you left the academia, you were a wonderful support when you worked here. Erika Roman, for all the knowledge that you willingly share about animals, without that, this the-sis would be full of caveats.
To all the members of the NAB-group, thanks for being great colleagues.
Lova, you are a fantastic person, who does so much for others. I don’t know a single person in the department who haven´t been helped by you. You de-serve the best. Stina and Nikita, it was good to have some familiar PhD-faces when coming back to the lab, keep up the good work. Victoria and Lena, for help and support with teaching and students. Åsa, for being an energy injec-tion! Marita, for all the help with animal work. Carin, for taking care of the everyday maintenance of lab stuff. Sam, a lot of fun left the lab when you headed back to England, you ́re missed! Sara and Loudin, thanks for intro-ducing and welcoming me as a new PhD student and for all the travelling to conferences! Shima, for being my light and laughter in the office for the first years. The distance between Norrland and Middle East has never been so small. To all the students who has helped me in my projects.
The Comasco-group, Erika, Aniruddah, Megha and Maria, for your hard work and fruitful discussions!
The staff in department of Pharmaceutical Biosciences for helping out with everyday problems. Especially to all PhD students, the past ones (Alfhild, Anna, Anneli, Erika, Helen, Inga, Jenny, Jonathan, Mats, Oskar, Patrik) for showing it is possible and to the present ones (Lisa (You go!), Erik, Sofia)
for doing it. Lena (O ́Raili) for being a reliable source of knowledge, the solid rocks in the department.
One “Blaj” a day keeps the doctor away! Shima, thanks for introducing me to the fantastic group of friends you have. That you having fantastic friends is off course no surprise! Emelie, you are wise, fun and helpful, what else can one ask for? Srebrenka, why didn’t we hang out more during the phar-macy program? I’m glad we had a second chance, I love the way you ap-proach life! Sahar, the sweetest and toughest person I know. Sofie, the calm-ness and the (positive) nerdicalm-ness of your personality are a perfect match.
Maria, your ability of being both superfun an superserious is amazing!
Jenny, Alexandra and Mikka, we are having a 12 (!) years anniversary this year. I hope our 2017-babies will share the same friendship.
To all the babies of the next generation (Alma, Abbe, Astrid, Evy, Iris, Greta and Sigge) that decided to be born around the time I was on maternal leave. I had so many great parents to hang out with because of you. I hope I can fol-low you through your lives. An extra thank to Abbe, it has been great to have your mom (Elin) to run beside in the last miles of the PhD-marathon.
To my family for being the foundation of my wellbeing, you are the best! I could not have asked for a better environment to grew up in, I really hope I can pass it forward. My PhD period would not have gone this smoothly without being raised of the master of organization and the lifestyle without procrastination, i.e., my mom. I have also tried to apply the calmness that my dad always brings to any situation. To know that the two of you always have my back makes it easier to go through life. My sister Erika for always (or at least before kids came into the picture…) having time to talk and analyzing things and for being inspiring in the way that you really loves your job, if every teacher were as you are there would not be any crisis in the Swedish school system! Per, you have been in our family for such a long time that I almost cannot recall the time before, I´m happy you are a part of “the Granholms”. Bastian, the families little whirlwind, your energy will take you far! My grandmother, the most inspiring 92-year old I know, if I will be half as you are in your age I will be happy. I love you all!
My own little family that I love so much. Tobias, for always letting me be me, for spoiling me with great food every day, letting me whine as much as I want, for always remembering me of the funny things in life and making me forget work as soon as I come home. Ebbe, my funniest person in the world, for you being you is the best thing I know. To see you grow up is a privilege, but please can we slow down the time for a while now!
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