Â鶹ÒùÔº

Anxiety, the psychological and physiological state characterized by an anticipation of potential threats and a heightened sense of vigilance, is regularly experienced by many humans worldwide. Research suggests that anxiety is a behavioral consequence of stress, designed to "prepare" humans for uncertainty and risky situations.

Yet excessive anxiety and a tendency to regularly avoid some situations to ease this anxiety can be detrimental, sometimes even leading to the development of so-called anxiety disorders. Understanding the evolutionary origins of anxiety, as well as its underlying neural and biological mechanisms, could be highly beneficial for the development of new treatments for anxiety disorders.

Past studies gathered evidence suggesting that anxiety is also experienced by other vertebrates (i.e., animals possessing a vertebral column and a skull), including mice, rats, primates, and even zebrafish. In contrast, the anxious behavior of invertebrates (i.e., animals without a vertebral column) has remained largely unexplored so far.

Researchers at the University of Modena and Reggio Emilia and other institutes recently carried out a study aimed at filling this gap in the literature by probing the existence of anxiety-like behaviors among invertebrates, specifically focusing on Lymnaea stagnalis, commonly known as great pond snails. Their paper, in Translational Psychiatry, demonstrates that great pond snails do exhibit anxious behaviors, which can be modulated using pharmacological drugs.

"We demonstrate that after being exposed to fish water, which simulates the presence of predators, pond snails (Lymnaea stagnalis) exhibit a series of sustained fear responses," wrote Veronica Rivi, Pierfrancesco Sarti, and their colleagues in their paper. "These include increased aerial respiration, changes in righting behavior, and reduced escape responses. Notably, these behaviors persist even after the stressor (fish water) is removed, indicating that they likely represent an anxiety-like state rather than a simple conditioned reflex."

As part of their recent study, Rivi, Sarti and their colleagues carried out a series of behavioral and pharmacological experiments involving pond snails. They exposed these snails to fish water (i.e., water that had previously contained fish), which eat snails and thus would be perceived as a threat by them.

Interestingly, they found that both while and after exposure to this fish water, the snails surfaced more frequently to breathe and appeared to take longer to flip themselves to an upright position. This suggests that they were anticipating the threat associated with fish, even if the fish were not actually in their surrounding environment.

"Exposure to fish water enhances long-term memory formation for the operant conditioning of aerial respiration, suggesting that the predator scent potentially induces a state of heightened alertness, which enhances memory consolidation processes," wrote Rivi, Sarti and their colleagues.

"Furthermore, when snails experience fish water alongside an appetitive stimulus (carrot), they form configural learning—a higher form of learning—where the appetitive stimulus now triggers a fear response instead of eliciting feeding. Importantly, the anxiolytic drug alprazolam prevents these anxiety-like responses."

After they observed anxiety-like behaviors in the pond snails, the researchers tried to mitigate them using a well-known anxiolytic drug. They found that the drug appeared to eliminate anxious behaviors, with higher doses producing greater effects.

"Through dose-response experiments, we found that alprazolam at a concentration of 0.1 µM for 15 min effectively counteracts predator-induced anxiety without causing sedation," wrote Rivi, Sarti and their colleagues.

"This treatment also prevents the effects of predator cues on learning and memory. However, consistent with data from vertebrates—alprazolam induces anterograde amnesia, impairing the formation of new memories for up to 3 h after treatment, though it does not cause long-term memory deficits."

The recent work by this team of researchers could open new possibilities for research focusing on anxiety, as it suggests that anxious behaviors are not limited to vertebrates and could also be studied in invertebrates. In the future, it could inspire other research groups to study the physiological and behavioral responses of pond snails, as well as other invertebrates.

"This is the first study showing that a molluscan model organism exhibits anxiety-like behaviors similar to those seen in vertebrates, and these behaviors can be mitigated by an anti-anxiety drug," wrote the authors. "This suggests that fundamental anxiety mechanisms are evolutionarily conserved across species. By using this simple invertebrate model, our research offers new insights into the biological basis of anxiety and sets the stage for future pharmacological studies."

© 2025 Science X Network