5-HT1A receptor agonism in the basolateral amygdala increases mutual-reward choices in rats

Abstract

Rats show mutual-reward preferences, i.e., they prefer options that result in a reward for both themselves and a conspecific partner to options that result in a reward for themselves, but not for the partner. In a previous study, we have shown that lesions of the basolateral amygdala (BLA) reduced choices for mutual rewards. Here, we aimed to explore the role of 5-HT_1A receptors within the BLA in mutual-reward choices. Rats received daily injections of either 50 or 25 ng of the 5-HT_1A receptor agonist 8-OH-DPAT or a vehicle solution into the BLA and mutual-reward choices were measured in a rodent prosocial choice task. Compared to vehicle injections, 8-OH-DPAT significantly increased mutual-reward choices when a conspecific was present. By contrast, mutual-reward choices were significantly reduced by 8-OH-DPAT injections in the presence of a toy rat. The effect of 8-OH-DPAT injections was statistically significant during the expression, but not during learning of mutual-reward behavior, although an influence of 8-OH-DPAT injections on learning could not be excluded. There were no differences between 8-OH-DPAT-treated and vehicle-treated rats in general reward learning, behavioral flexibility, locomotion or anxiety. In this study, we have shown that repeated injections of the 5-HT_1A receptor agonist 8-OH-DPAT have the potential to increase mutual-reward choices in a social setting without affecting other behavioral parameters.

Figure 1

Timeline of the behavioral experiments and schematic drawing of the prosocial choice task. (a) The period of behavioral testing started with 1 day of open field testing, followed by 16 days of testing in the PCT (partner and toy condition lasting 8 days each), 4 days of the magnitude discrimination test and ended with another day of open field testing. Note that rats received injections of either 8-OH-DPAT or a vehicle solution shortly before each behavioral testing session. (b) Schematic drawing of the PCT showing actor and partner opposite to each other in the respective choice compartments; adapted from an open-access article by Hernandez-Lallement et al. distributed under the terms of the Creative Commons Attribution Licence, with friendly permission from the authors. OF open field, PCT prosocial choice task, MDT magnitude discrimination task.

Figure 2

Representative examples of cannula tips in the BLA. (a) Magnified selection showing relevant parts of the BLA at AP 2.56 mm posterior to bregma. (b) Microphotographs taken at approximately AP 2.56 mm posterior to bregma showing the tips of the bilateral guide cannulas in a single microscopic slice. Guide cannulas were implanted in the BLA to allow repeated, precise injections of either 8-OH-DPAT or a vehicle solution. Please note that the respective slice of the 25 ng 8-OH-DPAT group is cut slightly asymmetrical on the AP plane. AP anterior–posterior, BLA basolateral amygdala, BLa anterior basolateral amygdala, BLp posterior basolateral amygdala, BLv ventral basolateral amygdala. Adapted from Paxinos and Watson.

Figure 3

Injections of the 5-HT_1A receptor agonist 8-OH-DPAT increased mutual-reward choices in the prosocial choice task. This figure shows the percentage of both-reward (BR) choices and the social bias score in the expression phase (session 5–8) in block 3 (trials 11–15). (a) After injections of 8-OH-DPAT, rats made a higher percentage of BR-choices compared to the vehicle control group, but there were no significant differences between rats that received 50 ng or 25 ng 8-OH-DPAT. Differences between groups were only evident in the partner but not the toy condition. (b) Unlike vehicle injections, 8-OH-DPAT injections (50 ng and 25 ng 8-OH-DPAT groups pooled) caused an increase in BR-choices in the presence of a conspecific, but a decrease in BR-choices in the presence of a toy. (c) The social bias score, quantifying the normalized difference in BR-choices between the partner and the toy condition, of rats receiving 8-OH-DPAT was significantly higher compared to the social bias score of rats that received a vehicle solution. a.u. arbitrary units, *p < 0.05, **p < 0.01. Data are shown as mean values ± SEM.