Domperidone interferes with conditioned disgust reactions but not taste avoidance evoked by a LiCl‐paired taste in infant rats

Pautassi, Ricardo Marcos; Arias, Carlos F.; Molina, Juan Carlos; Spear, Norman E.

doi:10.1002/dev.20288

Cited by 17 publications

(25 citation statements)

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“…SDS has been proven capable of promoting anti-fatigue, anti-cancer, anti-oxidant and anti-aging effects [25]. Rats have been found to exhibit taste avoidance and conditioned disgust reactions after stimulation with LiCl [26]. Concerning in vivo and in vitro TUNEL experiments, we found that the administration of LiCl improved dopaminergic neuron loss and prevented PC12 cells from apoptosis, and SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Han

Wen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

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Section: Discussionmentioning

confidence: 99%

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Han

Wen

et al. 2018

Cell Physiol Biochem

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“…These results suggest that, in the preweanling rat, ethanol may share some postabsorptive effects with LiCl. Emetic-like effects are critical for the expression of LiCl-mediated disgust reactions in the infant rat (Pautassi et al, 2008a). …”

Section: Conditioned Aversion Mediated By Ethanol In the Preweanlimentioning

confidence: 99%

Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model

Pautassi

Nizhnikov

Spear

2009

Neuroscience & Biobehavioral Reviews

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The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.

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“…BAC's half-life is approximately 4 hrs following i.p. administration of the drug in rats and it has been shown to become pharmacologically active within 15 min, [2,18]. Thirty min following the injections animals were simultaneously presented with two different bottles of SAC (0.3% and 0.6%, %w/v) for a 30 min period, and bottle switching occurred as described for CS presentation on Day 1, the First Taste Exposure Day.…”

Section: Resultsmentioning

confidence: 99%

“…Lithium chloride was chosen as a comparison measure since it is a more conventional and well-established US found in many other taste aversion studies [15,18-21]. If animals steadily decreased their SAC consumption to nearly zero over the three acquisition trials we could conclude that BAC was acting as an US.…”

Section: Resultsmentioning

confidence: 99%

“…Goudie and colleagues [40] also showed that conditioned nausea was not always the necessary mediator of drug-induced conditioned taste aversions. However, while avoidance to a novel tastant may be induced by both positively and negatively reinforcing drugs, a conditioned taste aversion induced by malaise inducing (negative reinforcing) properties will be coupled with the Lay-On-Belly (LOB) response [20] and conditioned disgust reactions such as chin rubs and gapes [18]. Although we did not record these conditioned disgust reactions, an argument that BAC may have induced malaise is strengthened by the observation that animals receiving SAC + BAC pairings continued to avoid the SAC into the EXT phase of the study even though they were not receiving any BAC injection during this phase.…”

Section: Discussionmentioning

confidence: 99%

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Baclofen alters gustatory discrimination capabilities and induces a conditioned taste aversion (CTA)

et al. 2011

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BackgroundStudies intending to measure drug-induced changes in learning and memory are challenged to parse out the effects of drugs on sensory, motor, and associative systems in the brain. In the context of conditioned taste aversion (CTA), drugs that alter the sensorium of subjects and affect their ability to taste and/or feel malaise may limit the ability of investigators to make conclusions about associative effects of these substances. Since the GABAergic system is implicated in inhibition, the authors were hopeful to use the GABA agonist, baclofen (BAC), to enhance extinction of a CTA, but first a preliminary evaluation of BAC's peripheral effects on animals' sensorium had to be completed due to a lack of published literature in this area.FindingsOur first experiment aimed to evaluate the extent to which the GABAB agonist, BAC, altered the ability of rats to differentiate between 0.3% and 0.6% saccharin (SAC) in a two bottle preference test. Here we report that 2 or 3 mg/kg (i.p.) BAC, but not 1 mg/kg BAC, impaired animals' gustatory discrimination abilities in this task. Furthermore, when SAC consumption was preceded by 2 or 3 mg/kg (i.p.) BAC, rats depressed their subsequent SAC drinking.A second experiment evaluated if the suppression of SAC and water drinking (revealed in Experiment 1) was mediated by amnesiac effects of BAC or whether BAC possessed US properties in the context of the CTA paradigm. The time necessary to reach an asymptotic level of CTA extinction was not significantly different in those animals that received the 3 mg/kg dose of BAC compared to more conventionally SAC + lithium chloride (LiCl, 81 mg/kg) conditioned animals.ConclusionsOur findings were not consistent with a simple amnesia-of-neophobia explanation. Instead, results indicated that 2 and 3 mg/kg (i.p.) BAC were capable of inducing a CTA, which was extinguishable via repeated presentations of SAC only. Our data indicate that, depending on the dose, BAC can alter SAC taste discrimination and act as a potent US in the context of a CTA paradigm.

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Domperidone interferes with conditioned disgust reactions but not taste avoidance evoked by a LiCl‐paired taste in infant rats

Cited by 17 publications

References 50 publications

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model

Baclofen alters gustatory discrimination capabilities and induces a conditioned taste aversion (CTA)

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