Cannabinoid and opioid modulation of impulsive behavior and drug addiction

183 Pages·2013·9.45 MB·English

Cannabinoid
a n d o p i o i d
C
a modulation
n
n of impulsive
a
b
in Cannabinoid behavior
o
i
d a n d d r u g

a
n
d addiction
a n d o p i o i d
o
p
i
o
i
d

m
m o d u l a t i o n
o
d
u
l
a
t
i
o
n of impulsive Uitnodiging

o
f

i
m
p nt Voor het bijwonen van de openbare
e verdediging van mijn proefschrift:
u m
l
s b e h a v i o r u
iv c
e do Cannabinoid and opioid modulation of
b n impulsive behavior and drug addiction
e i
h n
e
Occasionally, it happens to all of us: you speak out of turn during a meeting or you make a a n Op donderdag 14 maart 2013 om 13:45
v j
cobofe mhsahmvoieeonsr ,t e aavnneddn imtmhoomrueeg dhsip ayetoecui fir ecaaaclltiluzyea o ltlyfh aicmta ynponuuols tis vhaeoff uaoclrdtdin ot’tnh he(amavc.et iT nswgaoi dw eiitxt.ha Oomurp ty leofosu r oebfsu idyg ahaitnl)y -ealxinvpdee niimmsippvuue llsspiiavvieer ior a a n d d r u g snij-li uv11au0nr 5 di,n eA dVmersi jtaeeu Urldana imvvae.nrs ihteeitt ,h Doeo fBdogeelbeolauawn
n
choice (acting with disregard of long-term consequences), respectively. When somebody is
d
hyper-impulsive, this personality trait can negatively affect that person’s life. Failure to suppress
d Receptie na afloop.
impulsive behavior (failing impulse-control) is a well-known endophenotype in people suffering r
u
from Attention-Deficit/Hyperactivity Disorder (ADHD) or drug addiction, but also for instance g a d d i c t i o n
in people with a bipolar disorder (during the manic phases). Hyper-impulsivity results from
a
abnormal brain functioning. However, the exact malfunctions in the ‘impulsive brain’ to date d
d
remain largely unknown, thereby hampering effective treatment of this maladaptive behavior.
ic Joost Wiskerke
An important aim of this Ph.D. thesis was to gain more insight in the neurobiology of impulsivity. t
i
In addition, this thesis examines some aspects of the neurobiology of drug addiction, a o Contact:
n
psychiatric disorder that, as mentioned before, is in most patients characterized by impulse [email protected]
control-related problems, particularly during the abstinence phase when drug addicts have been
drug-free for some time and try to prevent relapse. By using rat behavioral models combined
Paranimfen:
with various pharmacological approaches, we have studied the neurobiology of impulsivity
J
and relapse to drug seeking, in search of putative ‘targets’ for novel medication against hyper- o Anouk den Braber
impulsivity and/or drug addiction. Thereby, we focused specifically on the cannabinoid and o ([email protected])
s
opioid neurotransmitter systems. t
Jelte Wouda
W
([email protected])
© is Joost Wiskerke
k
e
r
k
e
Coverdesign2.0.indd 1 22-1-2013 21:41:56
Cannabinoid
a n d o p i o i d

m o d u l a t i o n
of impulsive
b e h a v i o r

a n d d r u g
a d d i c t i o n
Binnenwerk.indd 1 23-1-2013 11:25:51
The research described in this thesis was conducted at
The department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical
Center, Amsterdam, The Netherlands
This research was financially supported by
The Dutch Top Institute Pharma, project T5-107-1
Printing of this thesis was financially supported by
Echo Pharmaceuticals B.V.
Med Associates Inc.
Microbiotech/se AB
Cover design, artwork and lay out: Sjoerd Antoon Mulder - www.samulder.nl
Printed by: Ipskamp Drukkers B.V.
ISBN: 978-94-6191-618-1
Copyright © J. Wiskerke ([email protected]), 2012. All rights reserved. No part of this thesis may be
reproduced, stored in a retrieval system, or transmitted in any form without prior permission from the author.
Binnenwerk.indd 2 23-1-2013 11:25:51
VRIJE UNIVERSITEIT
Cannabinoid and opioid modulation of
impulsive behavior and drug addiction
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad Doctor aan
de Vrije Universiteit Amsterdam,
op gezag van de rector magnificus
prof.dr. L.M. Bouter,
in het openbaar te verdedigen
ten overstaan van de promotiecommissie
van de Faculteit der Geneeskunde
op donderdag 14 maart 2013 om 13.45 uur
in de aula van de universiteit,
De Boelelaan 1105
door
Joost Wiskerke
geboren te Bergen op Zoom
Binnenwerk.indd 3 23-1-2013 11:25:51
promotor: prof.dr. A.N.M. Schoffelmeer
copromotor: dr. T. Pattij
Binnenwerk.indd 4 23-1-2013 11:25:51
leescommissie: dr. J.W. Dalley
dr. A.E. Goudriaan
dr. L.H. Parsons
prof.dr. A.B. Smit
prof.dr. L.J.M.J. Vanderschuren
prof.dr. D.J. Veltman
prof.dr. T.J. de Vries
Binnenwerk.indd 5 23-1-2013 11:25:51
Binnenwerk.indd 6 23-1-2013 11:25:51
Table of contents
Chapter 1
General introduction 11 - 38
Chapter 2
µ-Opioid receptors in the nucleus accumbens shell region
mediate the effects of amphetamine on inhibitory control
and not impulsive choice 41 - 61
Chapter 3
Cannabinoid CB1 receptor activation mediates the opposing
effects of amphetamine on impulsive action and impulsive
choice 65 - 84
Chapter 4
On the role of cannabinoid CB1 and µ-opioid receptors in
motor impulsivity 87 - 100
Chapter 5
Relapse to heroin and sucrose seeking is associated with
distinct patterns of in vivo endocannabinoid release in the
rat medial prefrontal cortex 103 - 121
Chapter 6
General discussion 125 - 137
References 141 - 163
Summary in Dutch
Nederlandse samenvatting 165 - 174
Acknowledgments
Dankwoord 175 - 178
Curriculum vitae 179
List of peer-reviewed publications 180 - 181
Binnenwerk.indd 7 23-1-2013 11:25:51
Binnenwerk.indd 8 23-1-2013 11:25:51
C h a p t e r 1
G e n e r a l
i n t ro d u c t i o n
Binnenwerk.indd 9 23-1-2013 11:25:51