Dopamine D1 receptor in the medial prefrontal cortex mediates anxiety-like behaviors induced by blocking glutamatergic activity of the ventral hippocampus in rats

The medial prefrontal cortex (mPFC) receives direct and indirect projections from the ventral hippocampus (VH) and plays an important role in the regulation of anxiety. However, the effect of the mPFC dopamine D1 receptor on anxiety-like behaviors induced by inhibition of glutamatergic activity in the VH has not been described. Here, we examined the effects of SKF38393, a selective dopamine D1 receptor agonist, on anxiety-like behaviors induced by NMDA receptor inhibition in the VH and neuron firing activity of mPFC. Injection of MK-801 (6 μg/0.5 μl) into the VH produced anxiety-like behaviors in the elevated plus maze and open field tests, increased the firing activity of pyramidal neurons in the mPFC, and decreased the level of dopamine in the mPFC. Injection of SKF38393 (0.5 μg/0.5 μl) into the mPFC produced anxiolytic effects, and normalized the hyperactive firing activity of mPFC pyramidal neurons induced by MK-801, whereas in both normal and anxiety-like rats caused by MK-801, injection of SKF38393 into the mPFC decreased the firing activity of mPFC interneurons but did not affect the dopamine content in the mPFC. The present data demonstrate that decreased D1 receptor activation in the mPFC may mediate anxiety-like behaviors induced by inhibition of glutamatergic activity in the VH. The balance of D1 receptor activity between pyramidal neurons and interneurons is a crucial factor in maintaining normal conditions, and inhibitory glutamatergic activity in the VH induces hyperactivity of mPFC pyramidal neurons through decreases in dopamine release and in the amount of D1 receptor activation on mPFC pyramidal neurons, which may be a critical factor for anxiety disorders.