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Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness‐inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre‐exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl‐induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model. [ABSTRACT FROM AUTHOR]

Background: One of the chemotherapy side effects on head and neck cancer patients is anticipatory nausea. However, the anticipatory nausea problem has not been properly resolved. Nausea might be psychologically reduced by hypnotherapy. There only have been very few studies conducted to examine the effects of hypnotherapy in alleviating anticipatory nausea. Purpose: This study aimed to determine the effect of hypnotherapy using Hanung induction technique on anticipatory nausea in head and neck cancer patients undergoing chemotherapy. Methods: This research employed a pre-post test of quasi-experiment with control group design. Consecutive sampling technique was used to obtain 64 subjects who met inclusion and exclusion criteria and were equally divided into the intervention and control groups. Hypnotherapy as the intervention was carried out in two sessions, each of which lasted for 20 minutes, with a week distance between sessions. The data were collected using a visual analog scale (VAS), which was used twice to measure anticipatory nausea and analyzed using the paired and independent-sample t-test. Result: The results showed that the mean score of anticipatory nausea in the intervention group reduced from 7.6±1.4 to 2.3 ±1.2 after hypnotherapy, while the mean in the control group increased from 6.4±1.6 to 6.7±1.4. There was a significant difference in the score of anticipatory nausea after the implementation of hypnotherapy between the intervention and the control group (p

The aim of this study was to assess the effectiveness of concealing the hydration fluid bottle in order to reduce the experience of anticipatory nausea and vomiting before chemotherapy treatment in pediatric hematology oncology patients undergoing chemotherapy treatment. The study was carried out as a randomized controlled clinical trial. The study was conducted sixty-two pediatric oncology patients who underwent chemotherapy in a hospital in Ankara, Turkey. The patients were randomly alloceted to an intervention group (n = 32) or a control group (n = 30). Patients in the intervention group concealing the hydration fluid bottle throughout the duration of hydration; patients in the control group received routine procedure (No concealment intervention) during hydration degree of nausea and vomiting were measured by the Baxter Retching Faces (BARF) scale. This study found no differences in the characteristics of the patients or in degree of nausea and vomiting between groups at enrollment. After concealing the hydration fluid bottle during the hydration, BARF scores were lower in the intervention group (p <.001). Concealing the hydration fluid had significant effects on degree of nausea and vomiting in pediatric oncology patient who received hydration before chemotherapy. This approach can be added as routine care as an effective non pharmacological intervention for pediatric oncology patient with receiving chemotherapy. • Interventions should be applied in children receiving chemotherapy in order to decrease anticipated nausea and vomiting. • It has shown that concealing the hydration fluid from those undergoing chemotherapy can decrease anticipatory nausea. • It can be considered a simple and applicable method for the management of the symptoms of nausea and vomiting in children. [ABSTRACT FROM AUTHOR]

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. • Disgust behaviours were conditioned to a context using LiCl (primary conditioning). • Secondary conditioning was produced by pairing the aversive context with a taste cue. • LPS attenuated the primary conditioning of context aversion. • LPS did not alter the secondary conditioning of context aversion or taste avoidance. [ABSTRACT FROM AUTHOR]

Background: One of the chemotherapy side effects on head and neck cancer patients is anticipatory nausea. However, the anticipatory nausea problem has not been properly resolved. Nausea might be psychologically reduced by hypnotherapy. There only have been very few studies conducted to examine the effects of hypnotherapy in alleviating anticipatory nausea. Purpose: This study aimed to determine the effect of hypnotherapy using Hanung induction technique on anticipatory nausea in head and neck cancer patients undergoing chemotherapy. Methods: This research employed a pre-post test of quasi-experiment with control group design. Consecutive sampling technique was used to obtain 64 subjects who met inclusion and exclusion criteria and were equally divided into the intervention and control groups. Hypnotherapy as the intervention was carried out in two sessions, each of which lasted for 20 minutes, with a week distance between sessions. The data were collected using a visual analog scale (VAS), which was used twice to measure anticipatory nausea and analyzed using the paired and independent-sample t-test. Result: The results showed that the mean score of anticipatory nausea in the intervention group reduced from 7.6±1.4 to 2.3 ±1.2 after hypnotherapy, while the mean in the control group increased from 6.4±1.6 to 6.7±1.4. There was a significant difference in the score of anticipatory nausea after the implementation of hypnotherapy between the intervention and the control group (p<0.001). Conclusion: The study concluded that hypnotherapy is effective in reducing the intensity of anticipatory nausea in head and neck cancer patients undergoing chemotherapy. Therefore, hypnotherapy can be applied by oncology nurses as an intervention in treating anticipatory nausea. [ABSTRACT FROM AUTHOR]

MTX is the medication most commonly used for antirheumatic treatment in juvenile idiopathic arthritis. It has high efficacy, is usually well tolerated and has an excellent safety profile. However, frequently intolerance symptoms develop that manifest as nausea, feelings of disgust or abdominal complaints prior to or directly after administration of the medication. No obvious toxicity is causing these intolerance symptoms, but symptoms are strictly limited to MTX and not transferred to other medications. MTX intolerance causes a significant reduction of quality of life in affected patients, frequently puts the treating physician in difficult situations regarding treatment choice, and may lead to uncomfortable decisions whether or not to stop an otherwise effective drug. Conventional countermeasures such as antiemetics, change of route from subcutaneous to oral or vice versa, or taste masking usually have only a limited effect. In this review, we present the current knowledge on MTX intolerance, its clinical picture and commonly employed strategies. We also consider newer behavioural treatment strategies that may offer a more effective symptom control. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a disease modifying anti-rheumatic drug commonly used to treat children with Juvenile Idiopathic Arthritis (JIA). Unfortunately, half of children taking MTX will experience MTX intolerance, which includes distressing gastrointestinal and behavioural symptoms associated with weekly MTX treatment. This qualitative study aimed to explore the perceptions of school-age children with JIA experiencing MTX intolerance, how they managed MTX intolerance, and how it impacted their daily life. An interpretive descriptive design was used. Twelve children participated in one individual 30-minute semi-structured interview using a storyboard technique to elicit their perceptions through storytelling. Interview transcripts and observational data collected during the interviews were analyzed using inductive content analysis. Children described MTX intolerance as extremely challenging. Three themes emerged from the data: (1) "No kid likes taking MTX". This theme was comprised of two subthemes related to: (a) associative MTX intolerance; namely, "Talking about it sometimes makes me feel sick"; and (b) anticipatory MTX intolerance, "Before [I take it], I have a little stomach ache". Other themes included: (2) The importance of strategies and routines; and (3) Working hard to live with MTX intolerance. This study sheds new light on MTX intolerance as perceived by school-aged children with JIA. Results highlight the importance of providing families and healthcare professionals with the necessary information for early recognition of MTX intolerance and optimizing care through the development of early intervention strategies. Study findings highlight the importance of prioritizing early identification and prevention of MTX intolerance. • Children are able to clearly describe their experience of MTX intolerance. • Children describe many triggers of MTX intolerance. • MTX intolerance is extremely challenging for children to live with. • Strategies and routines are very important for children in managing MTX intolerance. [ABSTRACT FROM AUTHOR]

Abstract The role of sex and estrous phase in the conditioning of toxin-induced disgust reactions (anticipatory nausea) to a novel context were examined in adult rats. Conditioned oral gaping responses have been shown to be a reliable index of nausea in rats. In Experiment 1 male and female rats were injected with LiCl (0, 64, 96, or 128 mg/kg) on each of 4 conditioning trials (72 h apart) and then placed in a novel context for 30 min. 72 h following the last conditioning trial each animal was re-exposed to this context in a toxin-free state for 10 min and disgust responses (gapes, forelimb flails, chin rubs, and paw treads) were scored from video records. A significant toxin dose-related monotonic increase in conditioned gaping showed a significantly greater increase in females, relative to males. In Experiment 2 female rats were conditioned, using the same paradigm, on either diestrus or proestrus days (trials 96 h apart) with LiCl (96 mg/kg) or saline control injections. Disgust responses were recorded on each of the 4 conditioning trials and a toxin-free test trial. Significant increases in conditioned disgust were obtained on proestrus relative to diestrus days on the toxin-free test trial. However no significant estrous cycle differences in disgust responding were obtained on the acquisition trials. The sex difference in conditioned gaping and the increased conditioned disgust responses in proestrus suggest that increased levels of estradiol likely enhance the strength of the association of the toxin-induced nausea with the novel context in rats. Highlights • Conditioned oral gaping responses are a reliable index of nausea in rats. • Female rats acquire higher levels of toxin-induced conditioned gaping to a novel context than males. • Female rats acquire higher levels of toxin-induced conditioned gaping to a novel context in proestrus relative to diestrus. • Higher levels of endogenous estradiol likely enhance the context conditioning of disgust responses in female rats. [ABSTRACT FROM AUTHOR]

This study examined sex differences in the establishment of lithium chloride (LiCl)-induced conditioned disgust behavior (anticipatory nausea) to a distinct context in adult male and female rats. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. Twenty-nine male and 31 female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200 μg/kg LPS or 0.9% (NaCl), 90 min prior to i.p. injections of either 128 mg/kg LiCl or 0.9% NaCl, and immediately placed into a distinctive context for 30 min (repeated over 4 conditioning days, spaced 72 h apart). 72 h following the final conditioning day, each subject was re-exposed to the context on a drug-free test day where orofacial and somatic behaviors were recorded. Results showed that LiCl-treated females conditioned stronger disgust reactions, relative to LiCl-treated males, as evidenced by significantly higher frequencies of conditioned “gaping” behavior ( p < 0.02) and forelimb flailing ( p < 0.01) in females. Pre-treatment with LPS during conditioning led to strong inhibition of conditioned disgust behavior, to levels that did not significantly differ from controls. Although there was no apparent sex difference in the degree of inhibition produced by LPS in this context-based rodent disgust model, males did exhibit significantly greater 24 h body weight losses following LPS injections on the first two conditioning days, relative to females. The results of the current study provide strong evidence for a sex difference in the establishment of anticipatory nausea, as well as, evidence for a sex difference in the acute-phase response to endotoxin treatment. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to update the 2011 recommendations for the prevention and treatment of anticipatory nausea and vomiting in children and adults receiving chemotherapy.Methods: The original systematic literature search was updated. Randomized studies were included in the evidence to support this guideline if they as follows: were primary studies published in a journal in full text (i.e., abstracts, letters, book chapters, and dissertations were excluded); published in English; evaluated an intervention for the prevention or treatment of anticipatory nausea and vomiting; reported the proportion of patients experiencing complete control of anticipatory nausea and vomiting consistently and; included at least ten participants per study arm for comparative studies and at least ten participants overall for noncomparative studies.Results: Eighty-eight new citations were identified. Of these, nine were brought to full-text screening; none met inclusion criteria. The guideline panel continues to recommend that anticipatory nausea and vomiting are best prevented through optimization of acute and delayed phase chemotherapy-induced nausea and vomiting control. Benzodiazepines and behavioral therapies, in particular progressive muscle relaxation training, systematic desensitization and hypnosis, continue to be recommended for the treatment of anticipatory nausea and vomiting.Conclusions: No new information regarding interventions aimed at treating or preventing ANV that met criteria for inclusion in this systematic review was identified. The 2015 MASCC recommendations affirm the content of the 2009 MASCC recommendations for the prevention and treatment of anticipatory nausea and vomiting. [ABSTRACT FROM AUTHOR]

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. • Lithium chloride can be used to model anticipatory nausea in rodents. • Lipopolysaccharide prevents anticipatory nausea acquisition. • Lipopolysaccharide impairs anticipatory nausea consolidation. • Lipopolysaccharide has no effect on the extinction of anticipatory nausea. • Immune stimulation can disrupt the learning and memory of conditioned disgust. [ABSTRACT FROM AUTHOR]

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. • Lipopolysaccharide (LPS) alters conditioned fear learning and memory. • LPS alters conditioned disgust learning and memory. • LPS can alter central processes via peripheral immune activation. • Immune activation within the hippocampus alters contextual memory. • Immune activation in the insula, amygdala, and area postrema alters illness memory. [ABSTRACT FROM AUTHOR]

Rationale: The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. Objective: The objective of this study was to determine the effect of combining subthreshold oral doses of Δ-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. Material and methods: The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. Results: For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Conclusions: Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients. [ABSTRACT FROM AUTHOR]

Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still problematic, with vomiting being somewhat better managed in the clinic. If post-treatment nausea and vomiting are not properly controlled, anticipatory nausea--a conditioned response to the contextual cues associated with illness-inducing chemotherapy--can develop. Once it develops, anticipatory nausea is refractive to current anti-emetics, highlighting the need for alternative treatment options. One of the first documented medicinal uses of Δ9-tetrahydrocannabinol (Δ9-THC) was for the treatment of chemotherapy-induced nausea and vomiting (CINV), and recent evidence is accumulating to suggest a role for the endocannabinoid system in modulating CINV. Here, we review studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system in human patients and pre-clinical animal models of nausea and vomiting. [ABSTRACT FROM AUTHOR]

Context: Anticipatory (prechemotherapy) nausea (AN) is a classic conditioned symptom not responding well to current antiemetics. Minimal work has been done to assess its risk factors and impact on chemotherapy-induced nausea and vomiting (CINV).Objectives: To evaluate risk factors for AN and assess its impact on CINV development.Methods: We analyzed data (n = 991) from a prospective observational multisite study in eight European countries over three cycles of chemotherapy. Patient/treatment characteristics were collected before chemotherapy. History of nausea/vomiting (yes/no), patient expectation of CINV (0-100 mm visual analog scale, [VAS]), and prechemotherapy anxiety (0-100 mm VAS) also were collected before chemotherapy. A patient-completed diary during each chemotherapy cycle obtained information on AN in the 24 hours before chemotherapy administration and nausea and vomiting (episodes of vomiting and severity of nausea) daily for five days after administration of chemotherapy (0-100 mm VAS).Results: AN was reported by 8.3%-13.8% of patients, increasing in frequency and intensity over each cycle. Every 1 mm increase in AN on the VAS was significantly associated with 2%-13% of increase in the likelihood of CINV (all P-values <0.05). Key predictors of AN in Cycle 1 included metastatic disease and prechemotherapy anxiety. However, predictors of AN in subsequent cycles included prechemotherapy anxiety and AN and CINV experience in the previous cycle, the latter being the strongest predictor (odds ratio = 3.30-4.09 for CINV outcomes over the cycles).Conclusion: AN is a challenging symptom, and its prevention needs to consider better CINV prevention in the previous cycles as well as managing prechemotherapy anxiety. [ABSTRACT FROM AUTHOR]

Rationale: Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. Objectives: This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Methods: Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. Results: CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HTR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. Conclusions: CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment. [ABSTRACT FROM AUTHOR]

Rationale: Δ-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. Objective: The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. Materials and methods: For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Results: Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Conclusions: Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning. [ABSTRACT FROM AUTHOR]

Objective: The high emetogenicity of chemotherapy results in cancer patients developing anticipatory nausea and vomiting (ANV). ANV is an example of classical conditioning which occurs as a result of associations between contextual cues in the hospital and chemotherapy-induced illness. In this study, we investigated the neural correlates of ANV by assessing c-Fos expression (a putative marker of neuronal activity) after conditioned context aversion (CCA) learning, an animal model of ANV that we have successfully developed. Methods: Twelve-week-old CD1 male mice were divided into two control groups; NaCl-Context B (n=18) and LiCl-Context A (n=18); and one experimental group LiCl-Context B (n=18). During conditioning, animals in the LiCl-Context A group received injections of LiCl in their home cages (Context A). Animals in NaCl-Context B and LiCl-Context B groups received injections of NaCl and LiCl in the conditioning context (Context B), respectively. Six animals of each group were perfused exactly 1 hour after the conditioning for the evaluation of c-Fos expression. CCA memory was tested with the remaining 12 animals in a 15-minute retention trial 72 hours after the conditioning. Amount of water intake was used as an index of aversion. Results: During the retention test, LiCl-Context B group exhibited significantly decreased water consumption compared to the controls (LiCl-Context A and NaCl-Context B), indicative of successful CCA development (p<0.001). c-Fos expression of LiCl-Context B group was significantly higher in the CA1-CA2 (p<0.001) and the dentate gyrus (DG) (p<0.001) subregions of the hippocampus compared to controls. Conclusion: The establishment of an association between a context and illness correlates with specific neuronal c-Fos expression within the CA1-CA2 and DG indicating a role for the hippocampus in the formation of CCA. Future studies should investigate the causal involvement of this brain region in the establishment of CCA. [ABSTRACT FROM AUTHOR]

Rationale: Fatty acid amide hydrolase (FAAH) inhibition elevates anandamide (AEA), which acts on cannabinoid (CB and CB) receptors, as well as N-palmitoylethanolamide (PEA) and N-oleoylethanolamine (OEA), which act on peroxisome proliferator-activated receptor alpha (PPARα). Here, we determine the mechanism of action of FAAH inhibition on acute and anticipatory nausea (AN). Objective: We compared the effectiveness and mechanism of action of two FAAH inhibitors, URB597 and PF-3845, to reduce acute nausea and AN in rodent models of conditioned gaping. Materials and methods: For assessment of acute nausea, rats were pretreated with vehicle (VEH), URB597 (0.3 and 10 mg/kg, experiment 1a) or PF-3845 (10 mg/kg, experiment 1b) 120 min prior to a saccharin-lithium chloride (LiCl) pairing. To assess the CB receptor or PPARα mediation of the effect of PF-3845 on acute nausea, rats were also pretreated with rimonabant or MK886, respectively. For assessment of AN, following four pairings of a novel context with LiCl, rats received a pretreatment of VEH, URB597 (0.3 mg/kg, experiment 2a), or PF-3845 (10, 20 mg/kg, experiment 2b) 120 min prior to placement in the AN context. To assess the CB receptor or PPARα mediation of the effect, rats were also pretreated with rimonabant or MK886, respectively. Results: PF-3845 (10 mg/kg, but not URB597 0.3 or 10 mg/kg) suppressed acute nausea via PPARα, but not CB receptors. URB597 (0.3 and 10 mg/kg) or PF-3845 (10 and 20 mg/kg) reduced AN via CB receptors, but not PPARα. Conclusions: FAAH inhibition reduces acute nausea and AN through PPARα and CB receptor mediated effects, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles. Methods: This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. Results: Five hundred ninety-eight patients (59 % female) were evaluable in cycle 2 (49 % HEC, 51 % MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3 %). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3 % before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95 % confidence interval (CI), 2.23-7.00; p < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. Conclusions: These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles. [ABSTRACT FROM AUTHOR]