Journal Article

Focal pharmacological manipulation of serotonin signaling in the amygdala does not alter social behavior

Waguespack, Hannah F., Forcelli, Patrick A., Campos-Rodriguez, Carolina, Maior, Rafael S., Jacobs, Jessica T., Malkova, Ludise

2025

Overview

Highlights Amygdala is proposed as site of action for serotonin drugs ameliorating anxiety. Contrary to this, intra-amygdala infusion of SSRIs did not affect social behavior. Similarly, 5-HT 1A , 5-HT 2A , and 5-HT 3 agonism/antagonism in amygdala had no effect. Thus, serotonin effects on social behavior are likely not modulated by amygdala. Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates. In rodents, acute systemic administration of drugs that increase serotonin signaling is associated with decreased social interactions. However, in primates, the direct involvement of serotonin signaling in the amygdala, particularly in affiliative social interaction, remains unexplored. Here, we examined the effects of serotonin manipulations within the amygdala on social behavior in eight pairs of familiar male macaques. We microinfused drugs targeting the serotonin system into either the basolateral (BLA) or central (CeA) amygdala and measured changes in social behavior. Surprisingly, the results demonstrated no significant differences in social behavior following the infusion of a selective serotonin reuptake inhibitor, 5-HT 1A agonist or antagonist, 5-HT 2A agonist or antagonist, or 5-HT 3 agonist or antagonist into either the BLA or CeA. These findings suggest that serotonin signaling in the amygdala does not directly contribute to the regulation of social behavior between familiar conspecifics. Future research should explore alternative mechanisms and potential interactions with other brain regions to gain a comprehensive understanding of the complex neural circuitry governing social behavior.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Agonists / Amygdala / Amygdala (Brain) / Amygdala - drug effects / Amygdala - metabolism / Animals / Behavior, Animal - drug effects / Biomedical and Life Sciences / Biomedicine / Cellular signal transduction / Conspecifics / Drug delivery / Drug interaction / Emotional behavior / Excitotoxicity / Health aspects / Interpersonal relations / Macaca mulatta / Male / Neural networks / Neurosciences / Original Investigation / Pharmacology/Toxicology / Psychiatry / Psychological aspects / Selective Serotonin Reuptake Inhibitors - pharmacology / Serotonin / Serotonin - metabolism / Serotonin Antagonists - pharmacology / Serotonin Receptor Agonists - pharmacology / Serotonin S1 receptors / Serotonin S2 receptors / Serotonin S3 receptors / Serotonin uptake inhibitors / Signal Transduction - drug effects / Social Behavior / Social interactions