- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- Neurochemical and behavioural correlates of glutamate...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
Neurochemical and behavioural correlates of glutamate and dopamine interaction in the rat nucleus accumbens Taepavarapruk, Pornnarin
Abstract
The present thesis examined whether activation of the ventral subiculum/cornu ammonis subregion 1 (vSub/CAl) area of the hippocampus by electrical stimulation can modulate the release of dopamine (DA) in the nucleus accumbens (NAc) and elicit locomotor behavior or drug seeking/taking behavior. The first series of experiments employed in vivo microdialysis technique with unanaesthetized rats, and confirmed that electrical stimulation of the vSub/CAl of the ventral hippocampus significantly increased extracellular DA efflux in the NAc and showed it was accompanied by an increase in locomotor activity. Pharmacological experiments revealed that the vSub/CAl-induced DA efflux in the NAc was mediated by ionotropic glutamate receptors (iGluRs) but not metabotropic glutamate receptors (mGluRs) group 1/2 in the NAc, whereas vSub/CAl-induced hyperlocomotion was mediated by glutamate receptors (GluRs) subtypes a-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate (AMPA/KA) and DA D1 receptors. The second series of experiments investigated other neural pathways that may contribute to vSub/CAl-induced DA efflux in the NAc. Transient blockade of neuronal activity in the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC) by lidocaine attenuated the evoked-DA release induced by vSub/CAl stimulation. Separate experiments found that GluRs in the VTA but not in the mPFC partially mediated these effects. Together, these findings suggest that vSub/CAl-induced DA efflux in the NAc may involve at least three possible neural pathways: a) presynaptic modulation of DA varicosities within the NAc; b) activation of PFC neurons; and c) GABAergic mechanisms in the NAc via the VP. The third series of experiments monitored dynamic changes in DA and DA metabolite efflux in the NAc during a continuous access-abstinence-relapse cycle of dextro-amphetamine (d-AMPH) self-administration in a 48 hr test session. These experiments confirmed previous reports that d-AMPH self-administration is associated with a significant increase in extracellular DA efflux in the NAc and that during abstinence, extracellular DA efflux in the NAc was decreased to values close to pre-drug baseline values. Electrical stimulation of the vSub/CAl, but not of the cortex, reinstated d-AMPH self-administration during abstinence and following extinction of drug-taking behavior. Electrical stimulation of the vSub/CAl again induced a significant increase in extracellular DA efflux in the NAc that coincided with reinstatement of d-AMPH-seeking behavior in rats. Pharmacological experiments revealed that reinstatement of drug-seeking behavior induced by vSub/CAl stimulation was blocked by either DA D1 or D2 receptor antagonists or the mixture of N-methyl-D-aspartate (NMDA) and DA D1 receptor antagonists. Taken together, the present findings provide further understanding of the neural circuits and specific GluRs and DA receptors responsible for vSub/CAl -induced DA efflux in the NAc, and behavioral activation. A possible role for the ventral hippocampus in facilitating relapse to drug seeking/taking behavior was also supported by experiments in this thesis.
Item Metadata
Title |
Neurochemical and behavioural correlates of glutamate and dopamine interaction in the rat nucleus accumbens
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2003
|
Description |
The present thesis examined whether activation of the ventral subiculum/cornu
ammonis subregion 1 (vSub/CAl) area of the hippocampus by electrical stimulation can
modulate the release of dopamine (DA) in the nucleus accumbens (NAc) and elicit
locomotor behavior or drug seeking/taking behavior. The first series of experiments
employed in vivo microdialysis technique with unanaesthetized rats, and confirmed that
electrical stimulation of the vSub/CAl of the ventral hippocampus significantly
increased extracellular DA efflux in the NAc and showed it was accompanied by an
increase in locomotor activity. Pharmacological experiments revealed that the
vSub/CAl-induced DA efflux in the NAc was mediated by ionotropic glutamate
receptors (iGluRs) but not metabotropic glutamate receptors (mGluRs) group 1/2 in the
NAc, whereas vSub/CAl-induced hyperlocomotion was mediated by glutamate
receptors (GluRs) subtypes a-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate
(AMPA/KA) and DA D1 receptors. The second series of experiments investigated other
neural pathways that may contribute to vSub/CAl-induced DA efflux in the NAc.
Transient blockade of neuronal activity in the ventral tegmental area (VTA) and the
medial prefrontal cortex (mPFC) by lidocaine attenuated the evoked-DA release induced
by vSub/CAl stimulation. Separate experiments found that GluRs in the VTA but not in
the mPFC partially mediated these effects. Together, these findings suggest that
vSub/CAl-induced DA efflux in the NAc may involve at least three possible neural
pathways: a) presynaptic modulation of DA varicosities within the NAc; b) activation of
PFC neurons; and c) GABAergic mechanisms in the NAc via the VP. The third series of experiments monitored dynamic changes in DA and DA
metabolite efflux in the NAc during a continuous access-abstinence-relapse cycle of
dextro-amphetamine (d-AMPH) self-administration in a 48 hr test session. These
experiments confirmed previous reports that d-AMPH self-administration is associated
with a significant increase in extracellular DA efflux in the NAc and that during
abstinence, extracellular DA efflux in the NAc was decreased to values close to pre-drug
baseline values. Electrical stimulation of the vSub/CAl, but not of the cortex, reinstated
d-AMPH self-administration during abstinence and following extinction of drug-taking
behavior. Electrical stimulation of the vSub/CAl again induced a significant increase in
extracellular DA efflux in the NAc that coincided with reinstatement of d-AMPH-seeking
behavior in rats. Pharmacological experiments revealed that reinstatement of
drug-seeking behavior induced by vSub/CAl stimulation was blocked by either DA D1
or D2 receptor antagonists or the mixture of N-methyl-D-aspartate (NMDA) and DA D1
receptor antagonists.
Taken together, the present findings provide further understanding of the neural
circuits and specific GluRs and DA receptors responsible for vSub/CAl -induced DA
efflux in the NAc, and behavioral activation. A possible role for the ventral hippocampus
in facilitating relapse to drug seeking/taking behavior was also supported by experiments
in this thesis.
|
Extent |
12642178 bytes
|
Genre | |
Type | |
File Format |
application/pdf
|
Language |
eng
|
Date Available |
2009-11-11
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
|
DOI |
10.14288/1.0091287
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2003-05
|
Campus | |
Scholarly Level |
Graduate
|
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.