Acetaminophen (paracetamol) affects empathy-like behavior in rats: Dose-response relationship

Empathy is the ability to recognize, process and respond to another's emotional state and empathic functions have been linked with a multitude of cognitive and affective processes. Impaired empathy has been linked to aggression and criminal behavior in society. Acetaminophen (paracetamol) is among the most common nonprescription (over the counter) analgesics in the world and has been already linked to reducing empathic behavior in humans. The aim of this study is to investigate the effects of acetaminophen on empathy-like behavior in Sprague Dawley rats, and we further explored the underlying mechanisms by analyzing empathy related neurohormones, e.g. oxytocin and vasopressin, in association with acetaminophen exposure in rats. Empathic behavior was assessed 30 min following acetaminophen administration (100, 200, and 400 mg/kg). The impact of single and repeated acetaminophen administrations on empathy-like behavior and anxiety level were evaluated separately. Empathy-like behavior was reduced with a single high dose of acetaminophen. Subsequent low dose administration of acetaminophen also reduced empathy-like behavior. In this study we also showed that acetaminophen decreased oxytocin and vasopressin levels in the prefrontal cortex and amygdalae. We found a negative correlation between delay in door opening time and measured prefrontal cortex oxytocin levels; we adjudged the latency in door opening time as enhanced empathic behavior which seemingly suggested the existence of a mechanism between empathy-like behavior and the prefrontal oxytocin. We observed that both a single high dose or repeated low dose administrations of acetaminophen reduced empathy-like behavior in correlation with a decrease in oxytocin and vasopressin levels in the prefrontal cortex and amygdala. Further research is needed to investigate the role of acetaminophen on the other empathic brain pathways.