LPS-Induced Garcia Effect and Its Pharmacological Regulation Mediated by Acetylsalicylic Acid: Behavioral and Transcriptional Evidence

SIMPLE SUMMARY: Using our Lymnaea stagnalis model systems and combining that with a Garcia effect training procedure, we studied novel aspects of this complex and highly conserved conditioned behavior and its pharmacological regulation. Injecting snails with lipopolysaccharide (LPS) 25 μg 1 h after snails experienced a novel taste caused snails to form a long-lasting Garcia-effect memory to avoid that specific taste. This effect was prevented by the pre-exposure of snails to acetylsalicylic acid (ASA) for 1 h before the LPS injection. Here, we researched the transcriptional effects of ASA and LPS in the snails’ central nervous system alone and in combination with naive snails. In a similar manner, the behavioral and molecular mechanisms causing the LPS-induced Garcia effect and its mitigation by ASA were studied. The LPS injections enhanced the expression levels of immune and stress response targets and enhancement was prevented by pre-exposure to ASA. Regarding genes associated with neuroplasticity, LPS by itself did not affect their expression levels. However, when combined with the Garcia-effect training procedure they were upregulated consistent with LTM formation. These findings suggest a conserved crosstalk between the immune and central nervous systems. ABSTRACT: Lymnaea stagnalis learns and remembers to avoid certain foods when their ingestion is followed by sickness. This rapid, taste-specific, and long-lasting aversion—known as the Garcia effect—can be formed by exposing snails to a novel taste and 1 h later injecting them with lipopolysaccharide (LPS). However, the exposure of snails to acetylsalicylic acid (ASA) for 1 h before the LPS injection, prevents both the LPS-induced sickness state and the Garcia effect. Here, we investigated novel aspects of this unique form of conditioned taste aversion and its pharmacological regulation. We first explored the transcriptional effects in the snails’ central nervous system induced by the injection with LPS (25 mg), the exposure to ASA (900 nM), as well as their combined presentation in untrained snails. Then, we investigated the behavioral and molecular mechanisms underlying the LPS-induced Garcia effect and its pharmacological regulation by ASA. LPS injection, both alone and during the Garcia effect procedure, upregulated the expression levels of immune- and stress-related targets. This upregulation was prevented by pre-exposure to ASA. While LPS alone did not affect the expression levels of neuroplasticity genes, its combination with the conditioning procedure resulted in their significant upregulation and memory formation for the Garcia effect.