Maintenance of conditioned place avoidance induced by gastric malaise requires NMDA activity within the ventral hippocampus

Abstract

It has been reported that during chemotherapy treatment, some patients can experience nausea before pharmacological administration, suggesting that contextual stimuli are associated with the nauseating effects. There are attempts to reproduce with animal models the conditions under which this phenomenon is observed to provide a useful paradigm for studying contextual aversion learning and the brain structures involved. This manuscript assessed the hippocampus involvement in acquiring and maintaining long-term conditioned place avoidance (CPA) induced by a gastric malaise-inducing agent, LiCl. Our results demonstrate that a reliable induction of CPA is possible after one acquisition trial. However, CPA establishment requires a 20-min confinement in the compartment associated with LiCl administration. Interestingly, both hippocampal regions seem to be necessary for CPA establishment; nonetheless, inactivation of the ventral hippocampus results in a reversion of avoidance and turns it into preference. Moreover, we demonstrate that activation of dorsal/ventral hippocampal NMDA receptors after CS–US association is required for long-term CPA memory maintenance.

Early‐life and chronic exposure to high‐fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges

“…The BLA is a key structure in the formation of aversive memories (McGaugh, 2013) and participates in COA formation (Sevelinges et al., 2009). The VHp is also involved in establishing aversive memories, particularly contextual (Hernández‐Matias et al., 2021) and odor aversion memories (Wang et al., 2013). Obesogenic diets are associated with impaired hippocampal activity (Bauer et al., 2015; Hernández‐Ramírez et al., 2021; Mestre et al., 2017).…”

“…Likewise, we observed enhanced glutamatergic and noradrenergic release within the VHp following administration of hypotonic LiCl. Although excitotoxic lesions of the VHp do not alter conditioned taste aversion acquisition and retrieval (Yamamoto et al., 1995), the activity within VHp is increased during the retrieval of COA (Dardou et al., 2006) and is involved in establishing LiCl‐induced conditioned place aversion (Hernández‐Matias et al., 2021). Hence, the VHp participates in aversive‐related memories, and HFD consumption alters the neurotransmission activity triggered by the administration of an aversive agent, possibly due to anxiety upregulation, as the VHp has been broadly associated with anxiety modulation (for excellent reviews, please see (Fanselow & Dong, 2010; Ghasemi et al., 2022)).…”

“…Hence, evidence suggests that obesity during adolescence is related to cognitive and executive dysfunctions (Mamrot & Hanć, 2019). Comparable results are observed in animal models of juvenile obesity; the consumption of high-fat diets (HFD) at weaning induces alterations in hippocampal plasticity (Hernández-Matias et al, 2021;Karimi et al, 2015;Khazen et al, 2019;Porter et al, 2012;Valladolid-Acebes et al, 2012, affecting spatial and relational memories (Boitard et al, 2012(Boitard et al, , 2014Hernández-Ramírez et al, 2021.…”