Background: It has generally been thought that serotonin release in the forebrain attenuates anxiety and impulsivity. However, there is so far no direct evidence proving this hypothesis because there has been no method that reversibly, selectively, and temporally-specifically controls serotonergic activity. In the present study, we aimed to obtaining direct evidence about the effects of acute serotonin release on anxiety and impulsivity using recently developed optogenetic tools.
Methods: We obtained transgenic mice expressing channelrhodopsin-2 (ChR2) mutant (C128S) only in central serotonergic neurons by crossing tetO-ChR2(C128S)-EYFP knock-in mice with Tph2-tTA BAC transgenic mice.
We applied blue light to the median raphe nucleus (MRN) to open ChR2, and recorded behavioral changes. The elevated plus maze was used to assess anxiety, and the 3-choice serial reaction time task (3-CSRTT) was used to assess impulsivity.
Results: Blue light illumination to the MRN increased anxiety-like behavior in the elevated plus maze test without affecting locomotor activity.
Optogenetic activation of serotonergic neurons in the MRN suppressed impulsive action without affecting other cognitive parameters in the 3-CSRTT.
Discussion: Although the present results regarding serotonin and anxiety are inconsistent with generally accepted hypothesis, our findings could account for why increased anxiety is sometimes observed during the initial phase of treatment of selective serotonin reuptake inhibitors (SSRIs).
As for impulsivity, serotonergic activation reduced impulsive action, consistent with generally accepted hypothesis. Thus, serotonergic activation of the MRN enhanced anxiety but suppressed impulsivity. Whether the serotonergic neurons involving in anxiety are different from those controlling impulsivity should be elucidated in future studies.