Date of Award
Doctor of Philosophy
The purpose of this study was to investigate, using electrophysiological and behavioural techniques, a mesolimbic dopaminergic mechanism in the accumbens that may regulate the hippocampal output signal transmission to the subpallidal area, and the pedunculopontine nucleus (PPN), an integral part of the mesencephalic locomotor region (MLR).;Electrical stimulation of the hippocampus activated accumbens neurones in urethane-anaesthetized rats. This excitation was attenuated by iontophoretic application of dopamine and by conditioning stimulation (10Hz) of the VTA. This attenuating effect was blocked by iontophoretic applied or intraperitoneally injected dopamine antagonists, as well as by 6-hydroxydopamine lesion of the VTA.;The excitability of the axonal terminals of the hippocampal-accumbens neurones was enhanced significantly by VTA stimulation, iontophoretic application of a dopamine D-2 agonist (LY171555) and potassium, but not by a dopamine D-1 agonist (SKF38393). This enhancement persisted after ibotenic acid lesion of the accumbens. Furthermore, the enhanced terminal excitability produced by VTA stimulation was prevented by iontophoretic application of a D-2 antagonist, sulpiride, but not by a D-1 antagonist, SCH23390.;Electrical stimulation of the hippocampus produced inhibitory responses in neurones of the ventral pallidal and subpallidal areas, the target sites of accumbens efferents. Some of these subpallidal neurones were also activated antidromically by stimulation of the PPN. The inhibitory responses were attenuated by microinjection of a glutamate antagonist, or by the dopamine D-2 agonist into the accumbens.;In unanaesthetized rat, locomotor responses elicited by unilateral microinjection of N-methyl-D-aspartic acid, an excitatory amino acid, into the hippocampus were reduced in by a D-2 agonist dose-dependently when injected into the medial accumbens. This hippocampal-initiated hyperkinetic response was also reduced by injecting nipecotic acid, a GABA uptake inhibitor, or procaine into the subpallidal area. Injection of procaine into the PPN also reduced significantly this hyperkinetic response.;Taken together these results suggest that excitatory signal transmission from the hippocampus to the accumbens was regulated presynaptically by a dopamine D-2 receptor mechanism. The hippocampal output signals, relayed via the accumbens, reached the subpallidal sites and descended to the PPN. This hippocampal-accumbens-subpallidal-PPN connection may enable hippocampal(limbic) signals to gain access to the MLR and elicit locomotor behaviours associated with biological adaptation.
Yang, Charles Renkin, "Dopamine D-2 Receptor Mechanisms In The Nucleus Accumbens Involved In Signal Transmission From The Hippocampus To The Mesencephalic Locomotor Region" (1987). Digitized Theses. 1619.