Effect of acute and subchronic administration of desipramine and venlafaxine on abuse liability of heroin in rats [Elektronische Ressource] / vorgelegt von Zofia Magalas

Hans Mustermann

Sujets

• Gesundheit

Informations

• Publié par: rheinisch-westfalischen_technischen_hochschule_-rwth-_aachen
• Publié le: 01 janvier 2006
• Nombre de lectures: 40
• Langue: Deutsch

Extrait

EFFECT OF ACUTE AND SUBCHRONIC
ADMINISTRATION OF DESIPRAMINE AND
VENLAFAXINE ON ABUSE LIABILITY OF HEROIN IN
RATS



Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der
Rheinisch-Westfälischen Technischen Hochschule Aachen zur Erlangung
des akademischen Grades einer Doktorin der Naturwissenschaften
genehmigte Dissertation

vorgelegt von
Zofia Magalas M. Sc.
Aus Ustrzyki Dolne, Polen


Berichter: Universitätsprofessor Dr. Hermann Wagner
Universitätsprofessor Dr. Werner Schmidt

Tag der mündlichen Prüfung: 15.11.2006




Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar
CONTENTS
CONTENTS ............................................................................................................................................... 1
LIST OF ABBREVIATIONS ................................................................................................................... 3
GLOSSARY................ 5
LIST OF ORIGINAL PUBLICATIONS................................................................................................. 7
INTRODUCTION...... 8
1.1 OPIATES.... 8
1.1.1 Acute and chronic effects of opiates: molecular level............................................................ 8
1.1.2 Effects of opiates; physiological and behavioural levels ..................................................... 11
1.1.3 Heroin .................................................................................................................................. 18
1.2 ANITIDEPRESSANTS............................................................................................................ 19
1.2.1 Antidepressants in therapy................................................................................................... 19
1.2.2 Antidepressants and addiction ............................................................................................. 22
1.2.3 Venlafaxine .......................................................................................................................... 23
1.2.4 Desipramine......................................................................................................................... 23
2 DESCRIPTION OF METHODS 24
2.1 CHOICE OF METHODS ................................................................................................................ 24
2.1.1 Self-administration............................................................................................................... 24
2.1.2 Conditioned place preference .............................................................................................. 35
2.2 CHOICE OF DRUGS..................................................................................................................... 38
2.2.1 Heroin .................................................................................................................................. 38
2.2.2 Antidepressants.................................................................................................................... 39
3 THE AIM OF THE STUDY........................................................................................................... 40
4 THE SEROTONIN/NORADRENALINE REUPTAKE INHIBITOR VENLAFAXINE
ATTENUATES ACQUISITION, BUT NOT MAINTENANCE, OF INTRAVENOUS SELF-
ADMINISTRATION OF HEROIN IN RATS ...................................................................................... 41
4.1 ABSTRACT................................................................................................................................. 42
4.2 INTRODUCTION ......................................................................................................................... 43
4.3 MATERIALS AND METHODS ....................................................................................................... 44
4.3.1 Subjects.44
4.3.2 Apparatus............................................................................................................................. 44
4.3.3 Surgery.. 45
4.3.4 Procedure 45
4.3.5 Data analysis ....................................................................................................................... 48
4.3.6 Drugs.... 48
4.4 RESULTS ................................................................................................................................... 48
4.5 DISCUSSION .............................................................................................................................. 52
15 THE TRICYCLIC ANTIDEPRESSANT DESIPRAMINE NON-SPECIFICALLY
ATTENUATES MAINTENANCE OF INTRAVENOUS SELF-ADMINISTRATION OF HEROIN
UNDER FIXED RATIO BUT NOT UNDER PROGRESSIVE RATIO SCHEDULE IN RATS..... 56
5.1 ABSTRACT................................................................................................................................. 57
5.2 INTRODUCTION ......................................................................................................................... 57
5.3 MATERIALS AND METHODS ....................................................................................................... 58
5.3.1 Subjects.58
5.3.2 Apparatus............................................................................................................................. 58
5.3.3 Surgery.. 58
5.3.4 Procedure 59
5.3.5 Data analysis ....................................................................................................................... 60
5.3.6 Drugs ................................................................................................................................... 60
5.4 RESULTS.... 61
5.5 DISCUSSION .............................................................................................................................. 63
6 EFFECTS OF VENLAFAXINE AND DESIPRAMINE ON HEROIN-INDUCED
CONDITIONED PLACE PREFERENCE IN THE RAT.................................................................... 66
6.1 ABSTRACT.. 67
6.2 INTRODUCTION ......................................................................................................................... 68
6.3 MATERIALS AND METHODS ...................................................................................................... 69
6.3.1 Subjects ................................................................................................................................69
6.3.2 Apparatus............................................................................................................................. 69
6.3.3 Procedures........................................................................................................................... 70
6.3.4 Drugs.... 71
6.3.5 Statistics 71
6.4 RESULTS.... 72
6.5 DISCUSSION .............................................................................................................................. 77
7 RESULTS – SUMMARY ............................................................................................................... 80
8 CONCLUSIONS 81
ACKNOWLEDGEMENTS .................................................................................................................... 82
CURRICULUM VITAE.......................................................................................................................... 83
BIBLIOGRAPHY.................................................................................................................................... 85

2LIST OF ABBREVIATIONS
5HT 5-hydroxy-tryptamine, serotonin
5-HT1-5HT5 serotonin receptors
α1, α2 adrenaline
AC adenylyl cyclase
ANOVA analysis of variance
A1 adenosine receptor or primary auditory cortex
ATP adenosine triphosphate
β1, β2 adrenaline receptors
BNST bed nucleus of the stria terminals
Ca2+ calcium
cAMP cyclic adenosine monophosphate
CNS central nervous system
COOH carboxyl group
CPA conditioned place aversion
CPP conditioned place preference
CREB cAMP response element binding protein
DA dopamine
DD drug discrimination
DLP dorsolateral pons
DRn dorsal raphe nucleus
ERK extracellular signal related kinase
FR fixed ratio
GABA γ-aminobutyric acid
GDP guanosine diphosphate
G protein GTP-binding protein
GTP triphosphate
GVG γ-vinyl GABA
i.m. intramuscularly
i.v. intravenous
i.p. intraperitoneal
IP3 inositol 1,4,5-trisphosphate
ICSS intracranial self-stimulation
IVSA intravenous drug self-administration
K+ potassium
3LC locus coeruleus
LTD long term depression
LTP long term potentiation
MAPK mitogen activated protein kinase
mPFC medial prefrontal cortex
mRNA messenger RNA
NA noradrenaline
NAcc nucleus accumbens
NH amino group 2
NMDA N-methyl-D-aspartate
NTS nucleus tractus solitarius
PAG periaqueductal grey
Pi phosphatidylinositol 3-kinase 3
PIP phosphatidylinositol 4,5-biphosphate 2
PFC prefrontal cortex
PGi nucleus paragigantocellularis
PKA protein kinase A
PKC phospholipase C
PO preoptic area
PR progressive ratio
Ras-GRF one of membrane protei