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Defense and antinociceptive responses can be elicited simultaneously by learned or innate danger signals when an organism is in imminent danger. Antinociception blocks the recuperative behavioral reactions following pain perception that could interfere with defensive efforts. Antinociception associated with fearful experiences involving a confrontation with a predator or a predator being in close proximity is well studied in mammals, but very little is known about how fear affects antinociception responses in fish. Antipredator behavior in Ostariophysan fish may be elicited by exposure to conspecific alarm substance (CAS) that can trigger a fear reaction. During the predator versus prey confrontation, the alarm pheromone system is activated and warns conspecifics about the assessment of predation risk. The purpose of the present study was to examine the possible activation of the endogenous analgesic system in Leporinus macrocephalus fish and to evaluate the modification of swimming activity induced by a nociceptive stimulus (i.e., a subcutaneous injection of 3% formalin) in fish that had previously been exposed to the CAS. The results show that formalin-mediated enhancement in swimming activity was significantly reduced after exposure to the CAS. This enhancement was blocked by naloxone (20mg/kg), which suggests that opioid signaling is involved. Therefore, we hypothesized that antinociceptive processes may occur in fish following exposure to a chemical substance that signals predation.