The effects of lipopolysaccharide (LPS) on conditioned disgust: Expanding the rodent model of lithium chloride (LiCl)-induced anticipatory nausea
Abstract
Anticipatory nausea is a classically conditioned response to cues previously associated with a nauseating stimulus. In rodents, this can be modelled by pairing the novel cue of a context with the toxic effects of lithium chloride (LiCl). This leads to conditioned disgust responses (indicative of anticipatory nausea, e.g. gaping) when exposed to the context alone. Selective immune activation using the endotoxin lipopolysaccharide (LPS) has emerged as a reliable way to attenuate anticipatory nausea prior to acquisition. However, there are gaps in our understanding of the effects of LPS during other memory stages known to be critical within the LiCl-induced anticipatory nausea paradigm. While expanding the rodent model of LiCl-induced anticipatory nausea, the current thesis aimed to investigate the role of LPS in attenuating these responses across consolidation and extinction. Upon reproducing the ability of LPS to attenuate LiCl-induced anticipatory nausea prior to acquisition, LPS was found to attenuate the consolidation of these behaviours when administered immediately after conditioning, and 24 h later, but not 72 h later within Chapters 2 and 3. These results suggest that specific memory stages are necessary to target for immune activation to attenuate anticipatory nausea. Although prior exposure to LPS did not significantly affect extinction, Chapters 2 and 3 established the extinction of LiCl-induced anticipatory nausea. Further, Chapter 3 demonstrated that LiCl-induced anticipatory nausea can be learned after long inter-trial intervals. These findings align with toxin-induced anticipatory nausea in humans and add to the validity of the current rodent model. In Chapter 4, second-order conditioning was established between an aversive context and a taste cue using the anticipatory nausea paradigm. Avoidance of the taste cue was examined in the two-bottle preference task. LPS attenuated conditioned disgust within the anticipatory nausea context but did not alter avoidance behaviours in the two-bottle task. The experiments presented in the thesis strengthen the rodent model of anticipatory nausea. Moreover, this thesis begins to provide an understanding of the mechanisms underlying LPS-induced anticipatory nausea attenuation by establishing the boundaries of the effects of LPS on these responses.