Activation of the central serotonergic system in response to delayed but not omitted rewards

Abstract

The forebrain serotonergic system is a crucial component in the control of impulsive behaviours. However, there is no direct evidence for natural serotonin activity during behaviours for delayed rewards as opposed to immediate rewards. Herein we show that serotonin efflux is enhanced while rats perform a task that requires waiting for a delayed reward. We simultaneously measured the levels of serotonin and dopamine in the dorsal raphe nucleus using in vivo microdialysis. Rats performed a sequential food-water navigation task under three reward conditions: immediate, delayed and intermittent. During the delayed reward condition, in which the rat had to wait for up to 4 s at the reward sites, the level of serotonin was significantly higher than that during the immediate reward condition, whereas the level of dopamine did not change significantly. By contrast, during the intermittent reward condition, in which food was given on only about one-third of the site visits, the level of dopamine was lower than that during the immediate reward condition, whereas the level of serotonin did not change significantly. Dopamine efflux, but not serotonin efflux, was positively correlated with reward consumption during the task. There was no reciprocal relationship between serotonin and dopamine. This is the first direct evidence that activation of the serotonergic system occurs specifically in relation to waiting for a delayed reward.

Fig. 1

Experimental apparatus and design of the sequential food–water navigation task. (A) The position of the microdialysis probe. (B) Open field and reward cylinders (food site, water site) for the task. Windows for nose-pokes (reward locations) are indicated. The dotted line represents the unmarked home-base circle that the rat was required to enter prior to reward site visits. (C) Schematic of each rat's movements required to receive rewards at both sites. (D) Actual, typical trajectories of a rat during the immediate, delayed and intermittent reward conditions. VTA, ventral tegmental area.

Fig. 2

Locations of the microdialysis probes in the DRN. Black bars represent the 2 mm length of the dialysis membranes. Numbers beside each plate correspond to mm from bregma. Coronal drawing modified from Paxinos & Watson (1998).

Fig. 3

Behavioural results of the sequential food–water navigation task. (A) Mean numbers of food pellets acquired during each reward condition. (B) Mean distance traveled during the three reward conditions. (C) Time between tone presentation and food site nose-poke. (D) Time between tone presentation and water site nose-poke. All error bars show + SEM (n=10). Asterisks indicate significant differences, as assessed by the paired t-test, *P<0.05, **P<0.01.

Fig. 4

Changes in 5-HT and DA efflux in the DRN during a task sequence. A typical example of 5-HT (A) and DA (B) efflux and behavioural measures during task sequence 2. (C) Number of food pellets acquired and (D) distance moved every 5 min during rest and task periods are plotted corresponding to 5-HT and DA efflux levels. Grey areas indicate the rest period, and dark grey areas are the rest periods used as the baseline.

Fig. 5

Average changes in 5-HT and DA efflux in the DRN during the three reward conditions. (A) Average time courses of 5-HT during the three reward conditions (n=10; ± SEM). The grey background shows the rest period. (B) Average time courses of DA during the three reward conditions (n=8; + SEM). (C) Average 5-HT levels during the 30 min task periods (n=10; + SEM). (D) Average DA levels during the 30 min task periods (n=8; + SEM). Asterisks indicate significant differences, as assessed by the Tukey’s HSD test, **P<0.01.

Fig. 6

Correlations between 5-HT and DA efflux and the number of food pellets. (A) Comparison between 5-HT and DA efflux. (B) Comparison between 5-HT efflux and the number of food pellets acquired in each 5 min sample period. (C) Comparison between DA efflux and the number of food pellets acquired in 5 min.