Dopaminergic neurotransmission has been implicated in the motor activating effects induced by the local infusion of NMDA in the ventral hippocampus (VH). The nucleus accumbens and the ventral tegmental area (VTA) have been proposed to be the main loci where dopamine is acting as a positive modulator of the VH NMDA receptor-mediated motor activating effects. However, the existence of a relatively high dopamine innervation and dopamine receptor density in the VH suggests the possibility of local dopamine/NMDA receptor interactions. This hypothesis was tested by studying the effects of the bilateral local VH infusion of NMDA (0.05, 0.1, 0.5 and 1.0 g/side), the dopamine D1/D5 receptor antagonist SCH 23390 (1 g/side) and the dopamine D2 receptor antagonist raclopride (1 and 5 g/side). Neither SCH 23390 nor raclopride induced any significant change in motor activity compared with the vehicle control group, but both compounds significantly antagonized the motor activation induced by NMDA. SCH 23390 (1 g/side) was more potent that raclopride (minimal effective dose: 5 g/side). These results demonstrate the existence of a strong tonic facilitating effect of dopamine, acting preferentially at dopamine D1/D5 receptors, on NMDA receptor-mediated effects in the VH.
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