Chemical stimulation of the ventral hippocampus elevates nucleus accumbensdopamine by activating dopaminergic neurons of the ventral tegmental area

Dual-probe microdialysis (with HPLC and electrochemical detection) in freel y moving rats and single-unit recording in anesthetized rats were used to s tudy the extent to which impulse flow through the ventral tegmental area (V TA) contributes to elevations in nucleus accumbens (NAS) dopamine (DA) evok ed by stimulation of the ventral subiculum (VS). During perfusion of artifi cial extracellular fluid into the VTA, injections of 0.74 mg of the excitat ory amino acid NMDA into the VS elevated accumbens DA to >150% of basal val ues. During intra-VTA perfusion of either 1 mu M tetrodotoxin (which blocks impulse flow) or 1 mM kynurenic acid (which blocks excitatory glutamate re ceptors), injections of NMDA into the VS failed to elevate accumbens DA. Th us, increased impulse flow through VTA DA neurons, mediated by excitatory g lutamate inputs to this region, appears critical for VS stimulation to elev ate NAS DA. Increased impulse flow through VTA DA neurons was confirmed usi ng single-unit recording in anesthetized rats. Intra-VS NMDA injections inc reased the firing rates of 45% (14 of 31), decreased the firing rates of 13 % (4 of 31), and had no effect on 42% (13 of 31) of VTA DA neurons. Increas es in firing rates were evident within 15 min of NMDA injections, a time at which VS NMDA injections elevate accumbens DA in awake animals. The result s of the present experiments identify the VTA as a critical site through wh ich outputs from the VS modulate NAS dopaminergic neurotransmission.