Conditioned Nausea Research Articles

Conditioned nausea induced by cisplatin and emetine identified by a taste reactivity test in rats

No prior studies have shown that gaping reactions are produced with the avoidance of conditioned taste caused by cisplatin and emetine. Therefore, we tried to demonstrate it using a taste reactivity test in rats and found the gaping reactions induced when saccharin is readministered after gustatory conditioning that paired saccharin with cisplatin or emetine. Since conditioned gaping reactions indicate the aversion to saccharin taste and conditioned nausea, the present study suggest that the taste aversion is induced by cisplatin and emetine. It was also found that with intraperitoneal injections of emetine alone, gaping almost never occurs.

Male and female rats exhibit comparable gaping behavior but activate brain regions differently during expression of conditioned nausea.

Twenty-five to fifty percent of patients undergoing chemotherapy will develop anticipatory nausea and vomiting (ANV), in which symptoms occur in anticipation of treatment. ANV is triggered by environmental cues and shows little response to traditional antiemetic therapy, suggesting that unique neural pathways mediate this response. Understanding the underlying neural mechanisms of this disorder is critical to the development of novel therapeutic interventions. The purpose of the present study was to identify brain areas activated during ANV and characterize sex differences in both the behavior and the brain areas activated during ANV. We used a rat model of ANV by pairing a novel context with the emetic drug lithium chloride (LiCl) to produce conditioned nausea behaviors in the LiCl-paired environment. We quantitated gaping, an analog of human vomiting, after acute or repeated LiCl in a unique environment. To identify brain regions associated with gaping, we measured c-fos activation by immunochemical staining after these same treatments. We found that acute LiCl activated multiple brain regions including the supraoptic nucleus of the hypothalamus, central nucleus of the amygdala, nucleus of the solitary tract and area postrema, none of which were activated during ANV. ANV activated c-fos expression in the frontal cortex, insula and paraventricular nucleus of the hypothalamus of males but not females. These data suggest that therapies such as ondansetron which target the area postrema are not effective in ANV because it is not activated during the ANV response. Further studies aimed at characterizing the neural circuits and cell types that are activated in the conditioned nausea response will help identify novel therapeutic targets for the treatment of this condition, improving both quality of life and outcomes for patients undergoing chemotherapy.

Characterizing Hedonic Responses to Flavors Paired with Internal Pain and Nausea through the Taste Reactivity Test in Rats.

Feeding behavior is a complex experience that involves not only sensory (i.e., visual, odor, taste, or texture) but also affective or emotional aspects (i.e., pleasure, palatability, or hedonic value) of foods. As such, behavioral tests that assess the hedonic impact of foods are necessary to fully understand the factors involved in ingestive behavior. In this protocol, we use the taste reactivity (TR) test to characterize the hedonic responses of rats to flavors paired with either lithium chloride-induced nausea or internal pain produced by hypertonic NaCl, two treatments that reduce voluntary consumption. This application of the TR test demonstrates how emetic and non-emetic (somatic pain in particular) treatments produce dissociable patterns of hedonic reactions to fluids: only emetic treatments result in the production of aversive orofacial responses, reflecting conditioned nausea, whereas somatic pain produces immobility, reflecting conditioned fear. Other methods, such as the microstructural analysis of licking behavior, do not reliably distinguish conditioned nausea and fear, a key advantage of the more selective TR procedure. This protocol also contains guidance for adaptation to other species and designs.

Conditioned hedonic responses elicited by contextual cues paired with nausea or with internal pain.

Pairing a taste with either internal pain or nausea, despite equivalent effects on voluntary consumption, has dissociable effects on hedonic responses: Only pairing with nausea results in the production of disgust reactions, while pairing with internal pain results in conditioned fear as indicated by immobility. Here, we use orofacial reactions to examine the hedonic responses elicited by contextual, nonflavor, cues paired with nausea produced by injection of lithium chloride (LiCl) or internal pain caused by injection of hypertonic saline. In Experiment 1, aversive orofacial responses were the specific context-elicited behaviors in the rats injected with LiCl, whereas immobility was seen in the animals injected with hypertonic saline. In Experiment 2, rats first received discriminative training with two contexts, where one context was paired with LiCl or hypertonic saline, and the other context with isotonic saline. After this, rats were intraorally infused with a flavor (conditioned stimulus (CS) +) in the paired context, and with a different flavor (CS-) in the unpaired context. Second-order conditioning was then examined in a test conducted in the unpaired context. The infusion of the CS + flavor produced aversive orofacial responses in the rats injected with LiCl but immobility in the subjects injected with hypertonic saline. The results suggest that nonflavor cues support conditioned hedonic responses in the same way as flavor cues, which implies that the quality of aversion learning (conditioned nausea vs. fear) is primarily determined by the nature of the aversive event and not the type of conditioned cue. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Overshadowing and latent inhibition in nausea-based context conditioning in humans: Theoretical and practical implications.

Volunteer participants underwent nausea-inducing body rotation in a distinctive context, and the acquired ability of the contextual cues to evoke nausea was subsequently assessed by a symptom rating scale. One group received prior exposure to the context (a latent inhibition procedure); a second consumed a novel flavour prior to rotation (an overshadowing procedure); a third group experienced both procedures; and a control group received neither. When tested in the context in the absence of rotation, all groups reported an increase in nausea-related symptoms at the time when rotation had previously occurred, an outcome consistent with the occurrence of conditioned nausea. The magnitude of this increase did not differ across the groups, but the overall level of responsiveness (the degree to which nausea-related symptoms were reported) was enhanced in the latent inhibition and reduced in the overshadowing condition. Cortisol levels showed the same pattern. The implications of these findings for the proposal that overshadowing and latent inhibition procedures might be used to control the development of anticipatory nausea in patients undergoing chemotherapy is considered.

Elevation of 2-AG by monoacylglycerol lipase inhibition in the visceral insular cortex interferes with anticipatory nausea in a rat model.

Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record

Learning pain-related fear: Neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain

Background and aimsThere exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS–US learning trials (“rapid conditioning”), and explored the underlying neural substrates of these learning and memory processes. MethodsIn N=24 healthy men and women, “rapid” fear acquisition was accomplished by pairing visual conditioned stimuli (CS+) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS−) were presented without US (differential delay conditioning with five CS+ and five CS− presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS–US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS+>CS−; CS+<CS−) was analyzed without and subsequently also with a linear parametric modulation including trial number as a regressor. ResultsA significant valence change (i.e. increased CS+ unpleasantness) was observed following acquisition, indicating successful differential aversive learning. On the other hand, CS–US contingency awareness was not fully established. These behavioral results were paralleled by differential activation of the putamen (pFWE<.05), insula (pFWE<.05) and secondary somatosensory cortex (S2, p<.001 uncorrected) in response to the CS+ during acquisition. The same analysis with a linear parametric modulation confirmed but also strengthened the resulting activations, which were all highly significant in ROI analyses at pFWE<.05. Extinction and reinstatement involved differential activation in response to the CS−, involving the cingulate cortex and primary motor cortex (M1) during extinction and the posterior cingulate cortex (PCC) during reinstatement (all p<.001 uncorrected), without obvious effects upon linear parametric modulation analysis. ConclusionsAbdominal pain stimuli are effective US that elicit conditioned pain-related fear even after very few learning experiences without full contingency awareness. These findings extend similar evidence of “rapid learning” in response to interoceptive US (e.g., conditioned taste aversion, conditioned nausea), and have implications for the pathophysiology and treatment of chronic abdominal pain such as in IBS.

Effects of overshadowing on conditioned and unconditioned nausea in a rotation paradigm with humans.

We examine whether overshadowing by salient stimuli is effective in reducing the ability of a certain environment (the putative conditioned stimulus) to evoke conditioned nausea in healthy humans that experience nausea-evoking rotation (as the unconditioned stimulus, US) in that environment. Twenty-four rotation-susceptible subjects (12 males, 12 females) were randomly assigned to receive either overshadowing by salient tasting beverages (OS+), or a control treatment (a familiar beverage, water; OS-) prior to rotation on three consecutive days (acquisition). To control for taste experiences, the alternative beverage was consumed 12h later in the home environment (OS+: water, OS-: salient beverage). At Day 4 (test), all subjects drank the familiar beverage (water) prior to rotation (US). Rotation was standardized as 2×1-min rotation/day. Nausea was determined by a 7-item symptom scale measuring symptom number (SN) prior to (anticipatory), immediately after, and 15 and 30min after rotation and by the Nausea Profile (NP) questionnaire immediately after rotation. Cortisol and tumour necrosis factor (TNF)-α in saliva were sampled at the same time-points. SN and cortisol were also measured at home. Overshadowing reduced anticipatory (conditioned) SN. Post-rotation nausea (i.e. the unconditioned response) measured by the NP decreased within the OS+ group only. Anticipatory cortisol and TNF-α were not affected by overshadowing. Treatment × gender interactions manifested for post-rotation cortisol and TNF-α. Groups did not differ in SN and cortisol at home. Overshadowing is effective in reducing symptoms of anticipatory nausea and rotation-induced unconditioned nausea; its effect on endocrine and immunological parameters is gender specific. Its application in alleviation of anticipatory nausea in cancer patients is considered.

Effect of 5-HT3 antagonists and a 5-HT1A agonist on fluoxetine-induced conditioned gaping reactions in rats

The effect of manipulation of the serotonin (5-HT) system on conditioned gaping (presumably reflective of nausea in rats) was evaluated. The potential of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (which produces nausea in the clinic), to produce conditioned gaping in rats and of the 5-HT(3) antagonists (ondansetron and palonosetron) and the 5-HT(1A) autoreceptor agonist (8-OH-DPAT) to reverse this effect were evaluated. In each of four experiments, rats received three pairings of intraorally delivered 17% sucrose solution and fluoxetine (0, 2, 10 or 20 mg/kg) and 72 h later were given a drug-free test trial. In experiment 2, rats were pretreated with the 5-HT(3) antagonists, ondansetron (0, 0.1 or 1.0 mg/kg) or the longer acting palonosetron (0.1 mg/kg), 30 min before each of three sucrose-fluoxetine (20 mg/kg) pairings. In experiment 3, rats were injected with palonosetron (0.1 mg/kg) 2 h before each of three sucrose-fluoxetine (20 mg/kg) or sucrose-lithium chloride (LiCl, 25 mg/kg) pairings. In experiment 4, rats were pretreated with the 5-HT(1A) autoreceptor agonist, 8-OH-DPAT (DPAT, 0.1 mg/kg) 30 min before each of three sucrose-fluoxetine (20 mg/kg) pairings. After two sucrose-fluoxetine pairings, the highest dose of fluoxetine tested (20 mg/kg) produced conditioned gaping reactions. These conditioned gaping reactions were prevented by pretreatment with DPAT, but not with the 5-HT(3) antagonists. On the other hand, palonosetron administered 2 h prior to sucrose-LiCl pairings attenuated conditioned gaping reactions. These results suggest that the conditioned nausea produced by SSRIs, but not LiCl, may be resistant to treatment with 5-HT(3) antagonists, but not 5-HT(1A) autoreceptor agonists.

Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.

Conditioned nausea in rats: Assessment by conditioned disgust reactions, rather than conditioned taste avoidance.

The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat drinks in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed using the taste reactivity (TR) test that includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned disgust reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Only treatments that produce nausea produce conditioned disgust reactions, but even rewarding drugs produce conditioned taste avoidance. Furthermore, treatments that alleviate nausea prevent the establishment and the expression of conditioned disgust reactions, but they do not necessarily modify conditioned taste avoidance. Considerable evidence exists indicating that these two measures can be independent of one another. The potential of a compound to produce conditioned disgust reactions is a reflection of its nausea-inducing properties. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but conditioned disgust is motivated by conditioned nausea.

Enhanced latent inhibition in context aversion conditioning

In four experiments, we investigated the effect of giving rats exposure to a distinctive environmental context before a phase of training in which an injection of LiCl was paired with that context. The results of Experiments 1 and 2 were consistent with the possibility that such preexposure served to retard subsequent conditioning to the context (i.e., produced a latent inhibition effect). Experiments 3 and 4 demonstrated that allowing the rats to consume a novel-flavored solution during preexposure enhanced the latent inhibition effect. The relevance of these findings both for theories of latent inhibition and for the use of preexposure as a clinical intervention for the reduction of conditioned nausea in humans is considered.

Role of classical conditioning in learning gastrointestinal symptoms

Nausea and/or vomiting are aversive gastrointestinal (GI) symptoms. Nausea and vomiting manifest unconditionally after a nauseogenic experience. However, there is correlative, quasiexperimental and experimental evidence that nausea and vomiting can also be learned via classical (Pavlovian) conditioning and might occur in anticipation of the nauseogenic event. Classical conditioning of nausea can develop with chemotherapy in cancer patients. Initially, nausea and vomiting occur during and after the administration of cytotoxic drugs (post-treatment nausea and vomiting) as unconditioned responses (UR). In addition, 20%-30% of cancer patients receiving chemotherapy report these side effects, despite antiemetic medication, when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea (AN) and/or anticipatory vomiting (ANV) and are explained by classical conditioning. Moreover, there is recent evidence for the assumption that post-chemotherapy nausea is at least partly influenced by learning. After summarizing the relevant assumptions of the conditioning model, revealing that a context can become a conditioned stimulus (CS), the present paper summarizes data that nausea and/or vomiting is acquired by classical conditioning and, consequently, may be alleviated by conditioning techniques. Our own research has focussed on two aspects and is emphasized here. First, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion-sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea and associated endocrine and immunological responses is summarized. Results from the rotation-induced motion sickness model showed that gender is an important moderator variable to be considered in further studies. This paper concludes with a review of the application of the demonstrated conditioning principles as interventions to ameliorate distressing AN/ANV in cancer patients undergoing chemotherapy, which is the second focus of our work.

Pavlovian conditioning of nausea and vomiting

Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25–30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-α were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.

Taste avoidance and taste aversion: evidence for two different processes.

The terms conditioned taste avoidance and conditioned taste aversion are often used interchangeably in the literature; however, considerable evidence indicates that they may represent different processes. Conditioned taste avoidance is measured by the amount that a rat consumes in a consumption test that includes both appetitive phases and consummatory phases of responding. However, conditioned taste aversion is more directly assessed with the taste reactivity test, which includes only the consummatory phase of responding. Rats display a conditioned taste aversion as conditioned rejection reactions (gapes, chin rubs, and paw treads) during an intraoral infusion of a nausea-paired flavored solution. Treatments that produce nausea are not necessary for the establishment of taste avoidance, but they are necessary for the establishment of taste aversion. Furthermore, treatments that alleviate nausea modulate neither the establishment nor the expression of taste avoidance, but they interfere with both the establishment and the expression of taste aversion. Considerable evidence exists indicating that these two measures are independent of one another. Taste avoidance may be motivated by conditioned fear rather than conditioned nausea, but taste aversion (as reflected by rejection reactions) may be motivated by conditioned nausea.

Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.

Rats display conditioned rejection reactions during an oral infusion of a flavor previously paired with an emetic drug; considerable evidence indicates that these rejection reactions reflect nausea. Here we report that cannabidiol, a major non-psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl homolog interfere with nausea elicited by lithium chloride and with conditioned nausea elicited by a flavor paired with lithium chloride. These results suggest that cannabinoids without psychoactive side-effects may have therapeutic value in the treatment of chemotherapy-induced nausea.

Lithium-induced context aversion in rats as a model of anticipatory nausea in humans

In three experiments, rats received injections of lithium chloride (LiCl) before being exposed to a distinctive context. In a subsequent test, rats given access to sucrose solution in this context consumed less than control subjects given sucrose in another context that had been paired with a saline injection (Experiment 1), or was quite novel (Experiment 2). Experiment 3 demonstrated that a context that had been associated with LiCl would serve to block the acquisition of a conditioned flavor aversion when it was presented immediately after the injection on a flavor–LiCl trial. These results show that a procedure in which rats experience the adverse effects of a lithium injection in the presence of contextual cues is effective in endowing those cues with aversive properties. It is argued that the context evokes a state of conditioned nausea, and the parallel with the clinical phenomenon of anticipatory nausea and vomiting (ANV) in human patients is outlined.

Effects of overshadowing on conditioned nausea in cancer patients: an experimental study

STOCKHORST, U., A. J. WIENER, S. KLOSTERHALFEN, W. KLOSTERHALFEN, C. AUL AND H.-J. STEINGRÜBER. Effects of overshadowing on conditioned nausea in cancer patients: An experimental study. PHYSIOL BEHAV 64 (5) 743–753, 1998.—The infusion of cytotoxic drugs in cancer patients is often accompanied by posttreatment nausea (PN). In addition, patients complain about nausea prior to an infusion [i.e., anticipatory nausea (AN)]. AN is mainly explained by classical conditioning, with the infusion as the unconditioned stimulus (US) and with the stimuli signaling the infusion as conditioned stimuli (CS). Despite this conditioning etiology, a specifically derived therapy to attenuate the CS-US contingency is missing. The purpose of this study is to develop and to test an overshadowing procedure for prevention of AN, and also for the modification of PN intensity. Sixteen cancer patients were assigned to one of two groups: Overshadowing + (OV+) and Overshadowing − (OV−). At the start of all infusions of two consecutive chemotherapy cycles A and B (acquisition), OV+ subjects drank a saliently tasting beverage (the overshadowing CS), whereas group OV− drank water. All patients received water in cycle C (test). Self-reported symptoms and heart rates were recorded. As expected, in cycle C (test), no patient of group OV+ showed AN, whereas two patients of group OV− developed AN. There was a tendency for a reduction of the intensity of PN, in terms of duration and latency after overshadowing, in cycle C: OV+ patients tended to show a shorter duration and a longer latency between end of infusion and PN onset. In OV−, there was a significantly larger heart rate deceleration in both measurement periods, in the anticipatory and the posttreatment measurement period. Data suggest to apply overshadowing for prevention of AN and modification of PN. Physiological markers of conditioned nausea are revealed. After its procedural implementation, the technique can be used in larger samples now.

Comparison of psychosocial adaptation of advanced stage Hodgkin’s disease and acute leukemia survivors

The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.

FACTORS MODIFYING THE RISK OF ACUTE AND CONDITIONED NAUSEA AND VOMITING IN OVARIAN-CANCER PATIENTS

We prospectively studied, how certain patient characteristics modify the risk of chemotherapy induced and conditioned nausea and vomiting. Young age and previous history of nausea and vomiting were factors associated with both chemotherapy induced nausea and vomiting as well as conditioned nausea. Conditioned nausea was significantly associated with having received two-day compared to one-day mode of chemotherapy, previous distress during blood samples and odor memory. Tentative associations were also found between a history of flushing and chemotherapy induced nausea and vomiting as well as between autonomic perception, odor associations and conditioned nausea. The investigated variables explained a larger part of the variance in conditioned compared acute nausea and vomiting.