Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist

5-HT1A receptor agonists increase the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and DA release in medial prefrontal cortex (mPFC). The mPFC is enriched in 5-HT1A receptors and projects to the VTA, where mesocortical dopaminergic neurons originate. We examined whether 5-HT1A receptor activation can modulate the activity of mPFC pyramidal neurons projecting to VTA. These were identified by antidromic stimulation from the VTA and were recorded extracellularly in anesthetized rats. The selective 5-HT1A agonist BAY × 3702 (10–80 μg/kg i.v.) increased the firing rate in 14/19 neurons (283 ± 79%) and reduced the activity of 5/19 neurons (22 ± 11%), resulting in an overall 2.2-fold increase of the firing rate. Both effects were blocked by the selective 5-HT1A antagonist WAY-100635. These results suggest that the increase in dopaminergic activity produced by 5-HT1A receptor activation can be driven by an increase in the activity of projection neurons in mPFC.