Regulation by 5-HT1A receptors of the in vivo release of 5-HT and DA in mouse frontal cortex

This study examines the effects of serotonin (5-HT)_1A receptor ligands on the in vivo release of 5-HT and dopamine (DA) in the prefrontal cortex of mice. Oral MKC-242 and 8-OH-DPAT, selective 5-HT_1A receptor agonists, decreased cortical 5-HT release at low and high doses, while the receptor agonists increased cortical DA release only at a high dose. Local application of the selective 5-HT_1A receptor antagonist, WAY100635, via a dialysis probe, antagonized oral MKC-242-induced increase in cortical DA release, but did not affect the decrease in cortical 5-HT release. Local application of 8-OH-DPAT at 100 and 300 nM via a dialysis probe increased cortical DA release, but did not affect cortical 5-HT release. The effects of oral MKC-242 and 8-OH-DPAT on 5-HT release were blocked by low and high doses of WAY100635, while blocking the agonist-induced increase in DA release required a high dose of WAY100635. These results suggest that 5-HT release and DA release in the frontal cortex of mice are regulated by pre- and postsynaptic 5-H_1A receptors, respectively, and that the presynaptic 5-HT_1A receptor-mediated response is more sensitive to inhibition by WAY100635 than the postsynaptic 5-HT_1A receptor-mediated response in mice.