Injections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens

The nucleus accumbens septi receives inputs from dopaminergic neurons of th e ventral tegmental area (VTA) and glutamatergic neurons of the ventral sub iculum (VS). The convergence of these inputs in the NAS is important for th e normal expression of exploratory locomotion; stimulation of the VS by inj ection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA) causes dopamine-dependent increases in locomotion. In the present study, in vivo microdialysis in conjunction with highperformance liquid chromatography and electrochemical detection (HPLC-EC) was used to estimate changes in extrac ellular dopamine in the VTA and NAS in response to intra-VS injections of N MDA (0.074, 0.28, 0.74 mu g). NMDA injections caused dose-dependent elevati ons in extracellular dopamine in each region. Each dose of NMDA clearly inc reased extracellular dopamine in the NAS, whereas only the two higher doses increased dopamine significantly in the VTA. The highest dose of NMDA elev ated extracellular dopamine to approximately 180% of baseline in each regio n. Whereas elevations in NAS dopamine might be induced by impulse-independe nt local mechanisms, elevations of dopamine in the VTA are presumed to refl ect increased somatodendritic release associated with increased impulse flo w through dopamine neurons. Thus, the present study suggests that the modul ation of dopaminergic neurotransmission by the ventral subiculum results fr om a trans-synaptic activation of dopamine cell bodies in the VTA. Synapse 31:241-249, 1999. (C) 1999 Wiley-Liss, Inc.