Neural circuits engaged in ventral hippocampal modulation of dopamine function in medial prefrontal cortex and ventral striatum

Dopamine (DA) transmission in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) is crucial for various cognitive processes. However, our understanding of the regulation of DA efflux by glutamatergic afferents to these areas is incomplete. Using microdialysis in freely moving rats, we provide evidence in the present study that brief stimulation (20 Hz, 10 s) of the ventral hippocampus potently increases DA efflux in the mPFC, NAc, and ventral tegmental area for 30–40 min. Subsequent experiments show that the stimulation-evoked increase in DA efflux in the mPFC depends on local activation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate, but not N-methyl-d-aspartate, receptors in the mPFC. Additionally, neural activity and ionotropic glutamate receptor activation in the ventral tegmental area are necessary for ventral hippocampal stimulation to increase mPFC DA efflux. Blocking neural activity or ionotropic glutamate receptors in the ventral tegmental area also attenuated the stimulation-evoked increase in DA efflux in the NAc. Evidence in support of a role for the mPFC in the stimulation-evoked increase in NAc DA was not obtained. Taken together, these observations highlight the important role of the ventral hippocampus in modulating forebrain DA efflux via separate neural circuits.