Neurochemical and behavioural correlates of glutamate and dopamine interaction in the rat nucleus accumbens.

摘要

The present thesis examined whether activation of the ventral subiculum/cornu ammonis subregion 1 (vSub/CA1) 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/CA1 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/CA1-induced DA efflux in the NAc was mediated by ionotropic glutamate receptors (iGluRs) but not metabotropic glutamate receptors (mGluRs) group1/2 in the NAc, whereas vSub/CA1-induced hyperlocomotion was mediated by glutamate receptors (GluRs) subtypes α-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/CA1-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/CA1 stimulation. Separate experiments found that GluRs in the VTA but not in the mPFC partially mediated these effects. Together, these findings suggest that vSub/CA1-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/CA1, but not of the cortex, reinstated d-AMPH self-administration during abstinence and following extinction of drug-taking behavior. Electrical stimulation of the vSub/CA1 again induced a significant increase in extracellular DA efflux in the NAc that coincided with reinstatement of d-AMPH-seeking behavior in rats. (Abstract shortened by UMI.)