Behavioural, neurochemical and neuroendocrine effects of predator stress in mice [Elektronische Ressource] / vorgelegt von Marjolein Beekman

Beekman, Marjolein

Sujets

• Gesundheit

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2004
• Nombre de lectures: 34
• Poids de l'ouvrage: 3 Mo

Extrait

BEHAVIOURAL, NEUROCHEMICAL AND
NEUROENDOCRINE EFFECTS OF
PREDATOR STRESS
IN MICE
















DISSERTATION


ZUR ERLANGUNG DES DOKTORGRADES
DER FAKULTÄT FÜR BIOLOGIE
DER LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN



VORGELEGT VON
MARJOLEIN BEEKMAN
MÄRZ 2004






BEHAVIOURAL, NEUROCHEMICAL AND
NEUROENDOCRINE EFFECTS OF
PREDATOR STRESS
IN MICE





DISSERTATION


FACULTY OF BIOLOGY
LUDWIG MAXIMILIANS UNIVERSITY MUNICH



SUBMITTED BY
MARJOLEIN BEEKMAN
MARCH 2004











































Betreuerin: Dr. Astrid C.E. Linthorst
1. Gutachter: Prof. Dr. Rainer Landgraf
2. Gutachter: Prof. Dr. Peter Schlegel

Dissertation eingereicht am: 10. März 2004
Tag der mündlichen Prüfung: 24. Mai 2004






TABLE OF CONTENTS 7

TABLE OF CONTENTS
SUMMARY.................................................................................................................10
ZUSAMMENFASSUNG.............................................................................................12
LIST OF ABBREVIATIONS.......................................................................................15
I. INTRODUCTION .........................................................................................17
1.Setting the scene.....................................................................................................17
1.1. Depression in society.............17
1.2. Etiology.............................................................................................18
2. Role of monoamines and stress in depression .....................................................20
2.1. Monoamines.........................................................................20
2.2. Stress and the HPA axis....................................................................21
2.2.1. Stress.............................................................................................21
2.2.2. The hypothalamus and the HPA axis...........................................22
2.2.3. Extrahypothalamic effects of CRH..........24
3. Anxiety disorders ............................................................................24
3.1.Forms of anxiety disorders..................................................24
3.2. Anxiety and depression.....................................................................26
4. Why this thesis?...............................................................................26
5.Behavioural animal models......................................27
5.1. The optimal animal model ...............................................................27
5.2. Animal models usedin depression research ............................................................28
5.3.Animal models used in anxiety research .................................................................29
5.4. Rats vs. mice........................................................................31
5.5. Genetic components...................................................31
5.6. Example: CRH-transgenic mice ..............................................................................32
5.7. Predator exposure.......................................................................................33
6. Neuroanatomy....................................34
6.1.The LHPA axis ..................................................34
6.2. Relevant brain areas in emotion and depression......................................................37
7. Neurotransmitters..............................................................40
7.1. Serotonin..................................................................................................................40
7.1.1. General...................................................................40
7.1.2. Involvement in stress, anxiety and depression.................43
7.2. Noradrenaline.....................................................................................44
7.2.1. General..........................................................................................44
7.2.2. Role in stress, depression and anxiety .............................45
7.2.3. Interactions between 5-HT and NA..............................................47
7.3. Dopamine.................................................................................................................48
7.3.1. General........48
7.3.2. Role in stress and depression...............................................................................50
8. Aims.........................................................................................................................50
II. MATERIALS AND METHODS....................................................................53
1. Experiments using microdialysis..........................................................................53
1.1.Microdialysis - Theoretical background...........................................53
TABLE OF CONTENTS 8

1.2. Microdialysis set-up.................................................................................................54
1.3. Overview of the experiments............................................................55
1.3.1. Animals and arrival.......................................................................56
1.3.2. Operation.......................................................................................57
1.3.3. Implantation of microdialysis cannula..........................................58
1.3.4. Predator exposure and killing .................................59
1.3.5. Histological verification.......................................................................................60
1.3.6. Video analysis.................................................................61
1.3.7. Analysis of dialysate – HPLC with electrochemical detection............................62
1.3.8. Measurement of free corticosterone – radioimmunoassay (RIA)........................64
1.3.9. Statistical analysis of behavioural data...................................................65
1.3.10. Statistical analysis of microdialysis data .....................................66
1.3.11. Statistical analysis of free corticosterone data........................................67
1.3.12. Other procedures and preparations ......................................................................68
2. Experiments measuring plasma levels of stress hormones ...................69
2.1.Overview of the experiments............................................................69
2.1.1. Animals, arrival and housing...............................................................................70
2.1.2. Rat exposure, killing, blood preparation..........................70
2.1.3. ACTH and corticosterone measurement..............................................................71
2.1.4. Behavioural analysis.....................................................................71
2.1.5. Statistical analysis........................................................................72
III. RESULTS ....................................................................................................74
1. Behaviour................................................................................................................74
1.1.Behaviour before rat exposure.................................................................................74
1.2. Behaviour during rat exposure....74
1.3.Behaviour after rat exposure......................................78
1.4. Differences in behaviour between C57bl/6N and Balb/c mice...................78
1.5. in behaviour on day 1 and 2 .................................................................79
1.6. Behaviour of rats..................................................................81
2. Microdialysis ............................................................81
2.1. In-vitro experiment ..................................................................................................81
2.2. Histological verification of probe location .......................................83
2.3. Serotonergic neurotransmission in C57bl/6N mice..........................84
2.3.1. Effect of rat exposure on 5-HT on day 1 .............................................................84
2.3.2. Effe 5-HIAA on day 1.........................................................86
2.3.3. Effect of rat 5-HT and 5-HIAA on day 2 ..........................86
2.4. Noradrenergic and dopaminergic neurotransmission in C57bl/6N mice.................87
2.4.1. Effect of rat exposure on day 1........................................87
2.4.2. Effe day 2........................................88
2.5. Serotonergic neurotransmission in Balb/c mice ......................................................89
2.5.1. Effect of r