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Pavlovian Conditioning of Taste Aversion Using a Motion Sickness Paradigm

From the Institutes of Medical Psychology (S.K., U.S.) and Psychology (A.R., E.K., Th.P.), Heinrich-Heine-University, Düsseldorf; Department of Internal Medicine (B.O., R.L.R.), University of Munich, Munich; and Department of General Surgery (P.E.), University of Tübingen, Germany.

Address for reprints requests to: Paul Enck, PhD, Zentrum Medizinische Forschung, Waldhörnle Str. 22, 72072 Tübingen, Germany. Email: paul.enck{at}uni-tuebingen.de

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: Pavlovian conditioning of taste aversion has rarely been investigated in healthy humans using motion sickness as the unconditioned stimulus (US).

METHODS: Ninety subjects were pretested for susceptibility to illusory motion (vection) in a rotating drum. Thirty-two subjects susceptible to pseudomotion were assigned randomly to two groups and received either water 1 hour before rotation and a novel taste (elderberry juice, conditioned stimulus, [CS]) immediately before rotation in a rotating chair (conditioning group), or the sequence of water and juice was reversed (control group). During the test session 1 week later, all subjects were exposed to water 1 hour before and juice immediately before rotation. The amount of liquids ingested, nausea ratings, rotation tolerance, and blood levels of hormones (ACTH, ADH, PP) were evaluated.

RESULTS: Subjects in the conditioning group developed taste aversion toward the novel taste, but not subjects in the control group. Postrotation nausea rating was affected marginally by conditioning, but rotation tolerance was not changed by conditioning. ACTH and ADH but not PP levels increased with rotation, but were unaffected by conditioning.

CONCLUSIONS: Pavlovian conditioning of behavioral, but not of endocrine, indicators was effective in susceptible subjects using a rotating chair as US and a single CS-US pairing.

Key Words: Pavlovian conditioning • taste aversion • motion sickness • nausea.

Abbreviations: ACTH = adrenocorticotrophic hormone; ADH = antidiuretic hormone; PP = pancreatic polypeptide; CS = conditioned stimulus; US = unconditioned stimulus; CNS = central nervous system; MSH = motion sickness history.

	INTRODUCTION

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Motion sickness occurs as a final result of a "central conflict" between different sensory inputs to the central nervous system (CNS) (1); this may be either visual-vestibular, visual-proprioceptive, or between any other two or more sensory systems involved (2), irrespective of the possible origins of the sensation. The severity of symptoms is said to be correlated with central and/or circulating levels of hormones and neuropeptides such as ACTH, ADH (vasopressin), and PP, but it is unknown whether increases of these biochemical markers indicate susceptibility to motion sickness or responsiveness to such a stressor (for review, see Ref. 3).

Pavlov introduced the procedure of classical conditioning (4) in which a conditioned stimulus (CS) is repeatedly paired with an unconditioned stimulus (US) eliciting an unconditioned response, and then the CS is tested alone for its ability to elicit the conditioned response. To rule out nonassociative factors, Rescorla (5, 6) argued that discriminative conditioning procedures provide appropriate control in conditioning designs, eg, tastes of which one (CS+) has been paired with the US and the other one (CS-) has not. These procedures have been used in animal taste-aversion learning studies (7, 8).

Conditioned taste aversion has also been established experimentally in humans using motion sickness as US (9, 10). These studies, however, did not use a discriminative conditioning procedure, as suggested by Rescorla. They also did not report to what extent subjects experienced rotation-induced nausea and vomiting and whether tolerance to rotation or pseudorotation was affected by conditioning. It has been proposed (11) that among the many forms in which nausea can occur in everyday life, some may be subject to classical conditioning as well. This at least has been shown for food aversions (12) and for anticipatory nausea in cancer therapy (13).

The present study uses a rotation-induced motion sickness paradigm to establish a conditioned taste aversion, using a differential conditioning paradigm as proposed by Rescorla (6). We examined the effects of conditioning on behavioral (taste aversion, rotation tolerance), subjective (nausea rating), and endocrine indicators of nausea (ACTH, ADH, PP). A test of a "herbal" drug (Eleutherococcus senticosus) putatively antiemetic similar to ginger (14) was included for its effects on rotation tolerance and rotation-induced nausea during the acquisition. It was expected that a salient CS+ previously paired with rotation would trigger conditioned taste aversion and would result in increased anticipatory nausea. We also expected an increase of the hormones said to be indicators of nausea on CS+ presentation. Based on previous results (15) of altered unconditioned nausea by a learning paradigm, we also expected that the salient CS+ would increase postrotation nausea and would reduce rotation tolerance.

	METHODS

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The study consisted of two parts: A prestudy to test susceptibility to illusory motion (vection) in a large group of volunteers, among whom subjects for the main study were recruited. In the main experimental study, susceptible subjects from the prestudy were assigned randomly to a conditioning group and a control group. The entire study was approved by the Human Subject Committee of the Heinrich-Heine-University Medical Institutions according to the Declaration of Helsinki, and subjects gave written, informed consent before participation.

Screening for Susceptibility to Motion Sickness (Vection-Drum Prestudy)
Ninety subjects (48 women, 42 men, 25.9 ± 4.6 years) were recruited from students of the Heinrich-Heine-University, Düsseldorf, by advertisement in teaching courses. At the initial visit, they were questioned about regular medical problems (blood pressure, allergies, medication) and whether they perform sport activities and/or consume alcohol and nicotine regularly.

They gave a history of their nausea experience with a self-developed motion sickness history (MSH) questionnaire. This test included 11 nausea-specific items mixed with 3 items unrelated to nausea experience (current vitality, somatization, anxiety). The 11 nausea items were: childhood merry-go-round preference; today enjoying a roller coaster; preference to test new fair attractions; ever experienced nausea while flying; ever experienced nausea while riding in a car; ever experienced nausea while riding in a train; ever experienced nausea on a boat or ship; ever experienced nausea with another condition; self-judgment as motion-sickness susceptible; experienced nausea within the last 8 weeks; and—women with children only—ever experienced nausea during pregnancy. All nausea-related questions were answered with either yes or no, and a sum score of positive answers was computed as the MSH score.

They were then seated in a vection drum designed with alternating horizontal black and white stripes at a 6-degree visual angle to induce illusory motion as previously described (eg, 16). The drum was rotated at a speed of 60 degrees per second around a fixed chair, which induces the impression of self-rotation, resulting in nausea in susceptible subjects. During rotation, the subjects were asked to keep their eyes open and to bend their heads up and down every 6 seconds to enforce nausea development by pseudo-Coriolis (the impression of a tumbling motion which is in conflict with the proprioceptive and vestibular CNS input) (1, 2). The procedure lasted for 10 minutes or until nausea forced them to ask for termination.

Subjects were subdivided into those who did or did not terminate the rotation procedure prematurely, and they were labeled "susceptibles" and "unsusceptibles," respectively. Before rotation and immediately afterward, nausea ratings were taken on the rating scale. This rating scale contained seven items (symptoms) related to nausea development: dizziness, headache, nausea, urge to vomit, tiredness, sweating, and stomach awareness. The items were taken from a 10-item scale developed by Graybiel et al. (17) which later had been modified by US and others (18) to account for the fact that some original symptoms did not allow self-ratings (eg, face skin color). Subjects gave their degree of severity of each single symptom on a visual analog scale between 0 and 5, and a sum score was computed.

Conditioning of Taste Aversion in Motion Sickness-Susceptible Subjects (Conditioning Study)
Thirty-two susceptible subjects recruited from the vection-drum prestudy population were randomly assigned to two groups (conditioning, control) ( Table 1). For 4 weeks before acquisition, half the subjects of each group received the putatively antiemetic substance, eleutherococcus (Elagen, Eladon Ltd., Bangor, UK) (400 mg/day tablet, twice daily), whereas the other half received a placebo in a double-blinded, randomized, and balanced fashion. For the acquisition and test, they had to fast overnight. Recording sessions were always in the morning, and for each subject, acquisition and test was at the same time of the day.

View larger version (17K): [in this window] [in a new window]   Fig. 1. Time sequence of CS presentations (CS+, CS-), nausea rating (R), blood sampling (B), intravenous catheter placement (C) and rotation during acquisition in the experimental conditioning group. In the control group, the sequence of water and juice was reversed. During the test session, both groups received water in the hospital and juice in the rotation chair. All other interventions were identical for both groups and at both occasions.

For rotation treatment, the subjects were seated in a rotating chair as previously described (21) and were exposed to 2-minute periods of constant rotation around the vertical axis (120 degrees/sec), during which they had to bend their heads up and down every 6 seconds with their eyes closed. Because the eyes are closed, the constant rotation is not perceived any longer—the semicircular canals of the vestibular system are only stimulated during acceleration and deceleration—so that vertical head movements induce a discrepancy between the true and the perceived motion, which is called Coriolis. This induces nausea in many subjects (1, 2). After a break of 2 minutes, this procedure was repeated for up to a maximum of five times or until subjects were not willing to proceed. The time (in seconds) that the subjects were able to accept rotation (ie, a maximum of 600 seconds) was noted and defined as rotation tolerance.

Hormonal measures were assessed from blood samples taken immediately before rotation and immediately after rotation termination. At each interval, a 10-ml blood sample was drawn for analysis using commercially available test kits for ACTH (Fa. Nicols, Bad Nauheim, Germany), ADH (Fa. IBL, Hamburg, Germany), and PP (22) by conventional radioimmunoassay. At the same time, as well as during each rotation break, severity ratings were taken for nausea symptoms on the above described scale. Nausea severity was calculated as the sum score across all items, and the mean scores achieved during rotation were evaluated and compared with baseline measures.

Testing
During the test phase 1 week later and at the same time of the day, all subjects received water 1 hour before rotation in the hospital environment and drank the juice immediately after being seated in the rotation chair. The amount of water and juice ingested before rotation was noted, the nausea rating was taken, and blood samples were drawn. Subjects then were rotated again in the above described fashion, and an additional rating and blood sample were taken after rotation termination. We applied rotation again to find out whether conditioning also would affect features of the unconditioned response (ie, postrotation nausea and rotation tolerance).

Statistical Analyses
In the screening prestudy, nausea ratings were compared before and after rotation within and between subgroups (susceptibles, unsusceptibles) by a 2 x 2 repeated measures ANOVA. Group comparisons were done by Student’s t test for interval scaled data and by chi-square test for frequency data.

In the conditioning study, a preliminary assessment of the potential effects of eleutherococcus on rotation tolerance and nausea symptoms at acquisition day revealed no antiemetic effects of the drug in comparison to placebo (t test for unpaired data: t = -0.91, p = .36 and t = 0.23, p = .81 for rotation time and nausea rating, respectively). Therefore, medication was excluded as predictor for additional analysis.

Group differences at acquisition day were tested by one-factorial ANOVAs with group (conditioning, control) as between factor. Correlations of nausea ratings to hormone levels were performed using Pearson’s correlation coefficient.

The effects of conditioning at test day were tested by 2 x 2 repeated measures ANOVAs for juice consumption, nausea rating, rotation tolerance, and blood hormone levels separately. Within-factor was repetition (acquisition, test), and between-factor was group (conditioning, control). Postrotation nausea and blood hormone levels were evaluated using a 2 x 2 x 2 ANOVA, adding pre- and postrotation as a second within factor. Correlations of pre- and postrotation nausea ratings with rotation tolerance time and postrotation nausea during acquisition were again performed as Pearson’s correlation coefficient.

All data are given as mean ± SEM. All tests were regarded as statistically significant when an alpha error margin of less then 5% was reached (23). Because of the pilot character of the study, p values were not corrected for multiple comparison.

	RESULTS

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Screening for Susceptibility to Motion Sickness (Prestudy)
Of the 90 subjects tested, 46 developed nausea and terminated the drum rotation after 348.9 ± 21.7 seconds, all the others were able to remain in the drum for the entire rotation time (a maximum of 10 minutes = 600 seconds). Rotation tolerance time of susceptibles ranged between 24 and 570 seconds. Age, gender, height, and weight were not different between susceptibles and unsusceptibles nor was the amount of sleep the night before. Susceptibles did not report more smoking, headaches, lowered or heightened blood pressure or a history of allergies, but did engage significantly less in sports than their unsusceptible counterparts and drank significantly less alcohol regularly. Susceptibles ranked significantly higher on the motion sickness history scale (MSH) ( Table 2).

Pavlovian Conditioning of Taste Aversion (Main Experimental Conditioning Study)
Of the 46 susceptible subjects from the screening study, 32 agreed to participate in the conditioning study. They were not different in any aspect from those susceptibles not recruited, except that they were available at the time of the study. Twenty-nine subjects finished the study, although 3 subjects prematurely dropped out (1 in the conditioning group, 2 in the control group) for personal reasons unrelated to the study, eg, availability. All subsequent data and analyses are based on 29 subjects.

Acquisition
No significant differences were found in juice and water consumption between the conditioning group and the control group before the first rotation ( Table 3). Prerotation nausea rating was significantly higher in the conditioning group when compared with the controls, but postrotation nausea and rotation tolerance were similar between both groups.

View larger version (14K): [in this window] [in a new window]   Fig. 2. ACTH, ADH, and PP levels (pmol/l) pre- and post-rotation during acquisition. Increases in ACTH and ADH were highly significant; no effect of rotation on PP levels.

Testing
At test day, subjects in the conditioning group consumed significantly less juice than in the control group (ANOVA, interaction effect "conditioning x repetition," F(1,27) = 17.01; p < .001) ( Figure 3A); they also consumed less water (Figure 3B), but this effect failed to reach statistical significance (F(1,27) = 3.35; p= .078). Control subjects did drink the same amount of both juice and water as during acquisition.

View larger version (19K): [in this window] [in a new window]   Fig. 3. Consumption of elderberry juice and water (in ml) during acquisition and at test day in the conditioning and the control group.

Prerotation blood hormone levels of ACTH and ADH were unaffected by conditioning, and postrotation increases of these hormones were only affected by rotation (main effect of rotation, F(1,27) = 5.06, p = .033 and F(1,27) = 6.45, p = .017, respectively).

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
We were able to show that a differential conditioning procedure using a salient taste paired a single time with nausea-inducing body rotation induced conditioned taste aversion in healthy volunteers. We found no change in prerotation nausea rating, either in the conditioning group or in controls. But anticipated nausea after CS+ exposure was significantly correlated to rotation-induced nausea severity during acquisition in the conditioning group, but not in controls.

This study not only confirms that Pavlovian conditioning is effective to induce taste aversion in healthy humans. It also extends previous reports by Arwas et al. (9) and Okifuji and Friedman (10) who used motion and illusory motion (vection), respectively, as the US. Although both experiments displayed development of taste aversion, they did not examine the effects on endocrine indicators of nausea and on rotation tolerance. We extended these studies by looking into whether conditioning would also affect the unconditioned response (rotation tolerance, postrotation nausea)—such effect was seen with data from an overshadowing study on conditioned nausea during cancer therapy (15) where treatment of anticipatory nausea in cancer patients by means of overshadowing also reduced the duration of posttreatment, unconditioned nausea. Postrotation nausea at test days was similar to acquisition in conditioned subject, but somewhat lower in control subjects. This may indicate that the latter exhibited some kind of habituation to the rotation procedure, which was prevented by conditioning of an aversive state in the conditioning group, thereby maintaining the level of postrotation nausea. However, this needs confirmation in a separate study.

This points toward the fact that nausea as unconditioned response may be an event in which both conditioned and unconditioned elements are combined. Although it needs additional experimental approval, this implies that behavioral approaches may also be effective in treatment of conditions as they may occur in many instances of everyday life. For posttherapeutic nausea in cancer treatment, this has been shown already by means of overshadowing (15). Other treatment options, eg, such as latent inhibition (19) still need to be evaluated.

In contrast to the salient CS+ paired with rotation in the experimental group, water paired with rotation did not become a relevant CS+ in the control because of its lack of salience, and was consumed by the control subjects at test day to a similar amount than during aquisition. In fact, the conditioning group did also drink less water at test day indicating some kind of generalization toward liquids, which could imply that the time interval of 1 hour between the CS- presentation and rotation may not be sufficient to prevent less drinking. However, inasmuch as the control subjects did not associate juice with the rotation procedure 1 hour later during the acquisition, we conclude that differential conditioning taste aversion according to Rescorla (5, 6) is feasible and effective in humans using motion sickness as US. For a complete counterbalanced design, the reversed sequence of stimulus A and B in the test session using two distinctive tastes rather than a salient and a nonsalient flavor would be needed in a future experiment; it may show that responses are only seen with CS+, irrespective of its particular properties.

Although we could demonstrate conditioning effects on a behavioral indicator of nausea (taste aversion), we could not find conditioning effects on circulating hormone levels that have been said to be indicative of nausea or nausea susceptibility. In an earlier study (24), we had found elevated nausea ratings and a—presumably compensatory—reduction of blood hormone levels of PP in anticipation to nauseogenic rotation after a first experience 2 days earlier, but this was not replicated here.

One reason for these conflicting findings might be that conditioning of hormonal effects does require more CS-US pairings than the one-trial exposure that is sufficient for taste aversion. Another explanation may be that circadian variation of hormone levels (25) may have obscured such effects to be seen in our study: Blood samples were taken in the early morning hours in our first study, but throughout the morning (although to identical times in each individual) in the current experiment. Furthermore, it may well be that conditioning effects on hormones may manifest at a different time scale after CS+ exposure than nausea, and therefore were missed with a single time-point assessment. If so, they were also confounded with the rotation-induced increase in hormone levels at test day. Finally, a 1-week interval between acquisition and test may be too long to identify conditioned endocrine changes. These arguments would favor changes in the experimental procedure in the future before a firm conclusion on the feasibility to condition nausea-relevant hormones can be drawn.

Alternatively, it may well be that the lack of an association between conditioned taste aversion and blood hormone levels indicates a dissociation between these two measures. ACTH, ADH, and PP have been said to be indicative of nausea severity and susceptibility (13). In many trials, they have been shown to respond to body rotation and nausea development, and exogenous ADH at supraphysiological doses, for instance, has been shown to mimic nausea development (26). It has remained an open question as to whether this reflects activation of the pituitary-adrenal axis or whether it may indicate its excitability. For example, clinical data have shown that salivary cortisol levels are elevated before chemotherapy in patients who develop nausea as compared with those who do not (27), and high baseline noradrenaline levels augmented delayed chemotherapy-induced nausea in adults (28). On the other hand, it is well established that many stress hormone levels peak late after stress onset or maximum (29), pointing toward a rather slow responsiveness of this system. Close monitoring of peripheral blood levels of these hormones during nausea development has recently (30, 31) supported the view that only ADH levels may correlate well with acute nausea experience. This is supported by the data reported here that subjects in the conditioning group exhibited elevated levels of subjective nausea and of ADH before rotation as compared with their counterparts both during acquisition and at test day. This baseline difference could have eliminated any potential effect of conditioning on ADH levels with rotation to become visible. The reason for increased baseline ADH (and nausea) in the conditioning group remains obscure, however. In summary, the effectiveness of a motion sickness paradigm for Pavlovian conditioning of behavioral markers, but not endocrine indicators, of nausea was shown.

	ACKNOWLEDGMENTS

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This work was supported by grants from DARA (50WB9548, 50WB9400) and DFG (En50/18, Pr264/1).

	NOTES

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Part of this work has been presented as a poster during the American Psychosomatic Society Annual Meeting, Vancouver, Canada, March 1999 and was published as an abstract (1999;61:88).

Received for publication January 29, 1999.

	REFERENCES

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1. Probst T, Schmidt U. The sensory conflict concept for the generation of nausea. J Psychophysiol 1998;12 Suppl 1:34–49.
2. Dichgans J, Brandt T. Visual-vestibular interaction: effects on self-motion perception and postural control. In: Held R, Leibowitz HW, Teuber HL, editors. Handbook of sensory physiology, vol. VII. Berlin: Springer: 1978. p. 755–804.
3. Reichardt B, Riepl RL, Lehnert P, Enck P. Endocrine changes in motion sickness. J Psychophysiol 1998;12 Suppl 1:50–5.
4. Pavlov IP. Conditioned reflexes. In: Anrep GV, editor and translator. New York: Dover Publications: 1960; originally published 1927.
5. Rescorla RA. Pavlovian conditioning and its proper control procedures. Psychol Rev 1967;74:71–80.
6. Rescorla RA. Pavlovian conditioning: it’s not what you think it is. Am Psychol 1988;43:151–60.
7. Klosterhalfen S, Klosterhalfen W. Conditioned taste aversion and traditional learning. Psychol Res 1985; 47: 71–94.[Medline]
8. Parker LA. Emetic drugs produce conditioned rejection reactions in the taste reactivity test. J Psychophysiol 1998;12 Suppl 1:3–13.
9. Arwas S, Rolnick A, Lubow RE. Conditioned taste aversion in humans using motion-induced sickness as US. Behav Res Ther 1989; 27: 295–301.[Medline]
10. Okifuji A, Friedman AG. Experimentally induced taste aversion in humans: effects of overshadowing on aquisition. Behav Res Ther 1992; 30: 23–32.[Medline]
11. Klosterhalfen S, Enck P. Nausea and vomiting—a multidisciplinary approach. J Psychophysiol 1998;12 Suppl 1:1–2.
12. Logue AW. Conditioned food aversion learning in humans. In: Braveman NS, Bronstein P, editors. Experimental assessment and clinical applications of conditioned food aversions. Ann NY Acad Sci 1985;43:316–24.
13. Bovbjerg DH, Redd WH, Jacobson PB, Manne SL, Taylor KL, Surbonew A, Crown JP, Norton L, Gilewski TA, Hudis CA, Reichman BS, Kaufman RJ, Currie VE, Hakes TB. An experimental analysis of classically conditioned nausea during cancer chemotherapy. Psychosom Med 1992; 54: 623–37.[Abstract/Free Full Text]
14. Grontved A. Brask T, Kambskard J, Hentzer E. Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol (Stockh) 1988; 105: 45–9.[Medline]
15. Stockhorst U, Wiener JA, Klosterhalfen S, Klosterhalfen W, Aul C, Steingrüber HJ. Effects of overshadowing on conditioned nausea in cancer patients: an experimental study. Physiol Behav 1998; 64: 743–53.[Medline]
16. Hu S, Grant WF, Stern RM, Koch KL. Motion sickness severity and physiological correlates during repeated exposure to a rotating optokinetic drum. Aviat Space Environ Med 1991;62:308–14.
17. Graybiel A, Wood CD, Miller EF, Cramer D. Diagnostic criteria for grading the severity of acute motion sickness. Aerospace Med 1968; 39: 453–55.[Medline]
18. Muth ER, Stern RM, Thayer JF, Koch KL. Assessment of the multiple dimensions of nausea: the nausea profile (NP). J Psychosom Res 1996; 40: 511–20.[Medline]
19. Lubow RE. Latent inhibition. Psychol Bull 1973; 79: 398–407.[Medline]
20. Stewart JJ, Wood MJ, Wood CD. Electrogastrograms during motion sickness in fasted and fed subjects. Aviat Space Environ Med 1989; 60: 214–7.[Medline]
21. Probst T, Dabrowski H, Liebler G, Wist ER. MARDER—Multi-axes rotation device for experimental research. J Neurosci Meth 1993; 49: 49–61.[Medline]
22. Riepl RL, Fiedler F, Ernstsberger M, Teufel J, Lehnert P. Effect of intraduodenal taurodeoxycholate and L-phenylalanine on pancreatic secretion and on gastroenteropancreatic peptide release in man. Eur J Med Res 1996; 1: 499–505.[Medline]
23. Borst J. Lehrbuch der Statistik. 2nd ed. Berlin: Springer; 1985.
24. Klosterhalfen S, Kuhlbusch R, Kugler J, Reichardt B, Riepl RL, Loose R, Probst T, Enck P. Rotating-chair induced motion sickness and anticipatory nausea. In: Brähler E, Schuhmacher J, editors. Psychologie und Soziologie in der Medizin. Gießen: Psychosozial Verlag; 1996. p. 93.
25. Jorde R, Burhol PG. Diurnal profiles of gastrointestinal regulatory peptides. Scand J Gastroenterol 1985; 20: 1–4.[Medline]
26. Caras SD, Soykan I, Beverly V, Lin Z, McCalllum RW. The effects of intravenous vasopressin on gastric myoelectrical activity in human subjects. Neurogastroenetrology 1997; 9: 151–56.
27. Fredrikson M, Hursti T, Fürst CJ, Steineck G, Börjeson S, Wikblom M, Peterson C. Nausea in cancer chemotherapy is inversely related to urinary cortisol excretion. Br J Cancer 1992; 65: 779–80.[Medline]
28. Fredrikson M, Hursti TJ, Steineck G, Fürst CJ, Börjeson S, Peterson C. Delayed chemotherapy-induced nausea is augmented by high levels of endogenous noradrenalin. Br J Cancer 1994; 70: 642–54.[Medline]
29. Richter SD, Schurmeyer TH, Schedlowski M, Hadicke A, Tewes U, Schmidt RE, Wagner TO. Time kinetics of the endocrine response to acute psychological stress. J Clin Endocrinol Metab 1996; 81: 1956–60.[Abstract]
30. Reichardt B, & örgil S, Riepl RL, Schedlowski M, Lehnert P, Enck P. ACTH- and ADH-profiles during motion sickness screened by continuous blood sampling. Gastroenterology 1997; 112: A811.
31. Reichardt B, Ayan T. Otto C, Klosterhalfen S, Riepl RL, Probst T, Lehnert P, Enck P. Short-term changes of ACTH and ADH levels during nausea development. Neurogastroenterology 1998; 10: 93.

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