Dopamine and serotonin interactively modulate prefrontal cortex neurons in vitro

Background. Dopamine (DA) and serotonin (5-HT) are released in cortex under similar circumstances, and many psychiatric drugs bind to both types of receptors, yet little is known about how they interact. Methods. To characterize the nature of these interactions, the current study used in vitro patch-clamp recordings to measure the effects of DA and/or 5-HT on pyramidal cells in layer V of the medial prefrontal cortex. Results. Either DA or 5-HT applied in isolation increased the evoked excitability of prefrontal cortex neurons, as shown previously. Coapplication of DA and 5-HT produced either a larger increase in excitability than when either was given alone or a significant decrease that was never observed when either was given alone. Dopamine or 5-HT also “primed” neurons to respond in an exaggerated manner to the subsequent application of the other monoamine. Conclusions. These data reveal the unappreciated interactive nature of neuromodulation in cortex by showing that the combined effects of DA and 5-HT can be different from their effects recorded in isolation. On the basis of these findings, we present a theory of how DA and 5-HT might synergistically modulate cortical circuits during various tasks.