I recently completed my doctoral degree in the field of Neuroscience, working at the interface between behavioural and cognitive neuroscience, immunology, and cancer research.
Co-supervised in the lab of Dr. Klaus-Peter Ossenkopp and Dr. Martin Kavaliers at Western University, my research focused on the development of a model of anticipatory nausea based on conditioned disgust behaviours and the influence of immune activation on these behaviours.
But what does that really mean? Anticipatory nausea is best explained within the context of chemotherapy. Chemotherapy is a cancer treatment that undeniably saves millions of lives worldwide. Yet, millions of treatable patients decide to drop out of this treatment. Why?
One of the reasons that people forego chemotherapy is due to conditioned nausea. Chemotherapy-induced conditioned nausea occurs when the hospital environment becomes associated, or paired, with the nauseating side effects of chemotherapy. Due to this association, patients re-entering the hospital often feel the need to vomit right when they step foot into the hospital. Imagine living with a life-threatening illness that can be treated, but just the sight of the treatment leaves you feeling nauseous. This is a painstaking reality for up to 45% of those diagnosed with cancer.
While anticipatory nausea is one of the most distressing side effects of chemotherapy, new and exciting developments in neuroimmunology are making strides to better understand and treat this learned response.
See my research in this area below (Bishnoi et al., 2022; Bishnoi et al., 2023; Bishnoi et al., 2024)
References
2024
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Lipopolysaccharide (LPS) attenuates the primary conditioning of lithium chloride (LiCl)-induced context aversion but not the secondary conditioning of context aversion or taste avoidance
Indra R Bishnoi, Martin Kavaliers, and Klaus-Peter Ossenkopp
Behavioural Brain Research, 2024
A first-order association can be formed between toxin-induced nausea and a context, as well as nausea and a taste cue. However, comparatively little is understood about second-order associations. The present study examined if the bacterial endotoxin, LPS, could impair the first- and second-order conditioning of context aversion (anticipatory nausea paradigm) and subsequent conditioned taste avoidance (two-bottle task). Adult male Long Evans rats were treated with LiCl (127 mg/kg, intraperitoneal [i.p.]) or vehicle control (NaCl) and then exposed to a distinct context for 4 first-order conditioning trials. LPS (200 μg/kg, i.p.) or NaCl were administered 24 h after each trial. Seventy-two h after the final first-order conditioning trial, rats underwent 2 second-order conditioning trials where they were treated with 2% saccharin (i.p.) and then exposed to the same context. Twenty-four h after the final second-order conditioning trial, rats were tested in a two-bottle task (2 trials), where they were given a choice between water and a palatable 0.2% saccharin solution. LiCl-treated rats demonstrated a context aversion by the 3rd conditioning trial in the anticipatory nausea paradigm. Rats previously exposed to LiCl also displayed a conditioned taste avoidance of saccharin within the two-bottle task. LPS attenuated first-order context aversion but did not alter either second-order context aversion or conditioned taste avoidance in the two-bottle task. This study demonstrated that a secondary association formed within an aversive context could result in a conditioned taste avoidance. Further, LPS may be able to attenuate primary conditioning, but not secondary conditioning.
2023
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Immune activation attenuates memory acquisition and consolidation of conditioned disgust (anticipatory nausea) in rats
Indra R Bishnoi, Martin Kavaliers, and Klaus-Peter Ossenkopp
Behavioural Brain Research, 2023
Anticipatory nausea is a classically conditioned response to cues (e.g. contexts) that have been previously paired with a nauseating stimulus, such as chemotherapy in humans. In rodents, anticipatory nausea can be modeled by pairing a novel context with lithium chloride (LiCl), which leads to conditioned disgust behaviours (such as gaping) when exposed to the context alone. Growing evidence suggests that selective immune activation attenuates various forms of learning and memory. The present study investigated the effects of the endotoxin lipopolysaccharide (LPS) on LiCl-induced anticipatory nausea across critical stages of associative memory including acquisition, consolidation, and extinction. Adult male Long Evans rats were subject to intraperitoneal (i.p.) LiCl (127 mg/kg) or vehicle control (NaCl) paired with a 30 min conditioning trial in a distinct context for a total of 4 trials. To study acquisition, rats were administered either LPS or NaCl (200 μg/kg, i.p.) 90 mins before the conditioning trials. To study consolidation, different rats were administered either LPS or NaCl (200 μg/kg, i.p.) immediately after the conditioning trials. These trials were followed by 4 drug-free extinction trials within the same context. LPS significantly reduced conditioned gaping behaviours by the 4th conditioning trial and on the 1st drug-free extinction trial when administered 90 mins before or immediately after the conditioning trials. LPS had no significant effect on extinction. The present study provides strong evidence for the attenuating effects of LPS exposure on the acquisition and consolidation of LiCl-induced anticipatory nausea.
2022
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Infection, learning, and memory: Focus on immune activation and aversive conditioning
Indra R Bishnoi, Caylen J Cloutier, Cashmeira-Dove Tyson, and 3 more authors
Neuroscience & Biobehavioral Reviews, 2022
Here we review the effects of immune activation primarily via lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, on hippocampal and non-hippocampal-dependent learning and memory. Rodent studies have found that LPS alters both the acquisition and consolidation of aversive learning and memory, such as those evoking evolutionarily adaptive responses like fear and disgust. The inhibitory effects of LPS on the acquisition and consolidation of contextual fear memory are discussed. LPS-induced alterations in the acquisition of taste and place-related conditioned disgust memory within bottle preference tasks and taste reactivity tests (taste-related), in addition to conditioned context avoidance tasks and the anticipatory nausea paradigm (place-related), are highlighted. Further, conditioned disgust memory consolidation may also be influenced by LPS-induced effects. Growing evidence suggests a central role of immune activation, especially pro-inflammatory cytokine activity, in eliciting the effects described here. Understanding how infection-induced immune activation alters learning and memory is increasingly important as bacterial and viral infections are found to present a risk of learning and memory impairment.