The mechanism(s) by which serotonin modulates dopamine release in the medial prefrontal cortex is not known, although studies suggest an involvement of 5-HT2 family receptors. We employed in vivo microdialysis and putatively selective 5-HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors are responsible for both drug-and stress-induced DA release in the medial prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated, for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or no affinity for non-5-HT2 receptors. Reverse dialysis with 5-HT2A antagonists had little or no effect on basal dopamine efflux. However, intracortical administration of MDL 11,939 or M100907 attenuated dopamine release induced by systemic administration of the 5-HT2 agonist DOI. Dual-probe microdialysis demonstrated that systemic DOI also increased glutamate concentrations in the ventral tegmental area (VTA). This was blocked by intracortical M100907. Cortical perfusion with M100907, or the atypical antipsychotic drug risperidone, but not the 5-HT2B/C ligand SB 206553, also decreased dopamine release induced physiologically by stress. These results indicate that stimulation of cortical 5-HT2A receptors increases the release of dopamine from the mesocortical system. They suggest that this effect may be mediated by increases in glutamate release from corticotegmental projections to the VTA. Additionally, they indicate that cortical 5-HT2A receptors modulate evoked dopamine release, such as that observed physiologically following mild stress. These findings may have implications for the pharmacological treatment of disorders resulting from or exacerbated by stress.

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The piriform cortex in homing pigeons receives a projection from the olfactory bulb and is necessary for the operation of those aspects of the navigational map based on olfactory stimuli in these animals. The afferent and efferent projections of the piriform cortex were studied using retrograde migration of wheat-germ agglutinin horseradish peroxidase (WGA-HRP) and Fast Blue, and anterograde migration of WGA-HRP. The piriform cortex was found to receive projections from, and send projections to, numerous regions and nuclei in the telencephalon, diencephalon and lower brainstem. A reciprocal connection with the parahippocampal region suggests that the piriform cortex and hippocampal formation may be part of a neural system that regulates navigational map learning. The piriform cortex also connects reciprocally with a large portion of the anterior telencephalon, including the cortex prepiriformis and hyperstriatum dorsale. In general, the pathway connections of the piriform cortex in homing pigeons are similar to those of the piriform cortex in mammals.