UBC Theses and Dissertations
UBC Theses and Dissertations
Neurochemical and behavioural correlates of glutamate and dopamine interaction in the rat nucleus accumbens Taepavarapruk, Pornnarin
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.
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