Nutritional Applications of the Chemical Senses Michael Naim' and Morley R. Kare Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104 Two of the major nutritional roles of oral sensory mechanisms are to initiate eating and to ensure reliable control of nutrient intake. Lepkovsky stated that the "universality of the chemical senses is best explained by the fact that in order to eat, the organism must possess some chemical knowledge" (I ). Studies have demonstrated that experimental animals, under some circumstances, are able to associate the sensory qualities of foods with their postabsorptive consequences, allowing the animals to select nutrients according to their physiological needs ( 2 4 ) . This suggests survival value of the chemical senses in governing selection of nutrients. However, at least in the industrialized nations, humans select and consume nutrients from among foods which are available in excess of survival needs. Additionally, taste experiences and cultural factors produce new eating patterns and nutritional consequences. Thus, the role played by the chemical senses during the over-consumption of high-salt, high-fat, and high-sugar foods becomes an obvious aim of nutritional studies. ntmuse oral stimulatiun cnn initiate exucrine and endwrine sca:rrtions invdvrd in dinestion and metabulism ( 5 61, at" tention is currently being given to the nutritional conseouences of these . nhvsioloeical secretions. In this paver, we " discuss possible nutritional applications of the interrelationshios of the chemical senses with eating behavior, digestion, and metabolism. The Role ot the Chemical Senses in Regulating the Selection of Nutrients It is apparent that the chemical senses play a significant role in food choices. The fact that newborn infants with no prior taste experience prefer sugar solutions over water in a pattern similar to that of adults, coupled with the fact that newborns show no preference for othertaste stimuli (9,lo), suggeststhat the human preference for sweet tastes is probably innate. The avid selection of sugar solutions by the human newborn
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Permanent address: The Hebrew University of Jerusalem, Faculiy
of Agriculture, Rehovot, P.O. Box 12, ISRAEL.
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complements their continuing caloric need. On the other hand, there is no apparent selection of sodium chloride solutions presumably because maternal milk is well supplied with sodium chloride. The newborn has a narrow margin of safety from dehydration stemming from the high ratio of surface area to body mass. Further, the ability to handle salt is limited because of the immature kidnev. A few vears later the child will select salty foods; however, by thattime the threat of dehydration is reduced and kidneys are fully functional. It would appear that, in the newborn, taste for sugar and for salt functions in the interest of the baby's welfare. When given a choice of novel foods, rats initially select diets having flavors known to appeal to humans in preference to diets containing tastes considered to he aversive. This unlearned discrimination may have survival value in mammals, since appealing tastes are associated with nutritious foods and many toxic compounds are bitter. The physiological state of an animal may induce altered behavioral patterns in food selection. For example, adrenalectomized rats develon huneer for salt. and so. a snecific . dium-deficient rats immediately selectsodium from among other cations (2. 11). This nhenomenon mav he a result of peripheral changrs in taste perception, as demonstrntrd by elrctrut)hssioluriral rewrdinrs from thr chordn t\mviu~inerve of rats, which Huggest t h a t t h e sodium-depleted ;at is less sensitive to the taste of NaCl(l2). Human subjects placed on a low sodium diet for 24 days rated a high NaCl concentration in soup as tasting less intense and more pleasant compared with pre- and post-experimental diets (13). In other preference tests, human subiects normallv preferred a 5% sucrose julution over a :Wosol;tinn hut nndd be indured toprefrr thr : N u b solutim after hlood rlurose levels uere rxl)er~mrntally decreased to 50 mg per i00 ml following insdin injection (14).
I t appears that, in some cases, the organism learns to associate the sensory quality of a food with its post-ingestional effects; this has been termed "specific hunger." Rats deficient in B vitamins learned to select the diet containing these vi-
tamins from amone several choices (3). Rats have also learned to prefer solutionsUcontainingspecific amino acids when fed a diet deficient in essential amino acids (4). Our laboratorv has demonstrated (15) that rats change theirinitial short-term preference for an appealingly flavored diet preferring to an adversely flavored diet if the latter is of greater nutritonal value (Fig. 1). It is interesting that wild rats (and fowl) are more responsive to the nutritive consequences of their selections than are their domestic counterparts. Such alterations in eating patterns serve as a survival mechanism, since they ensure selection of nutrients according to physiological needs. However, these mechanisms, which are, in many cases, demonstrable in experimental animals, do not sewn I" be as effective in humans. Should it he concluded that humans lack the basic mechanism for diet selection mediated hv nhvsioloeical feedback and that animals are therefore a " poor model for studying human eating hehavior? To address this problem, a distinction should he made between eating hehavior displayed under conditions of nutrient deficiencies and eating behavior in circumstances where essential nutrients exceed physiological needs. This distinction between deficient and suoolemental situations was recentlv discussed with respect tb'salt taste (13). Most available animal data on diet selection comes from studies involvineex~erimentallvinduced deficiencies, hut the oral sensation offood may play ;different role when excess nutrients are available. In supplemental situations, food availability and cultural ronditioninr can dominate food choices (16, 171. For example, Indian laborers, whose diets contain sour foods, rated citric acid as pleasant in direct proportion to its concentration (18). Conversely, Indian mediial students, who are accustomed to Western cuisine, rated citric acid as aversive in a pattern similar to that found in Western populations (19). Previous experience has also been found to play a role in the food selection hehavior of animals. Exposing rats to citric acid during weaning significantly increased the ingestion of citric acid a t a later aee. - , comnared with controls exoosed to citric acid after weaning or not previously exposed to citric acid a t all (20). Furthermore. tastes transmitted to infant rats throueh their mothers' milk affected food preferences in the post-weaning period (21).
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Food intake and Eating Behavlor While the chemical senses help to ensure regulation of diet selection in some deficiency or emergency situations, oral factors may play only a limited role in governing quantity of food consumed under these conditions. For example, regula-
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200 300 TIME (h ) Fog18 1 Pleference lest ot a a!eI rontalnong raw soybean protams(low nubd.ve value)mlxed woVl appealtng level oi D 35% soalum saccharm (0) vsrrusadlet containing heated soyDean poteins (him nubilive value) mixed wim havmive . are the mean and SEM of 12 rats. taste, 2.0% sucrase octaacetate ( 0 ) Values (Adapted from (15)).
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tion of food intake has been reported without the oropharyngeal factors in rats trained to feed themselves by pressing a lever which delivers liquid food into the stomach (22). Similarly, for a single meal fed intragastrically to human volunteers, the rate of food intake and the amounts consumed were identical to the results obtained with oral feeding (23). When an experimental diet was adulterated with an aversive taste stimul"~,after a short initial periud ne~thergrowmg (24) nor adult rats (25)reduced their fgxd intake; the rrdured food t intake and wei~htloss ubserved in rats given n d ~ eaddteratrd with the bittrr tasteufqumine (26)mav nut bedue tosensorv properties alone (see ref. (27)). sensory adaptation or habituation to an aversive taste may allow the animal to consume nutrients according to physiological needs; caloric deficit signals are evidently more important than aversive taste in feedine hehavior. However. when oossible habituation was hy daily variation of the-aversive taste in the diet among four aversive stimuli, growing rats ate 1%20% less than controls fed an unadulterated diet (28). taste. ad libitum caloric intake In the case of an anoealine .. was not elevated when a pr&rrtd runcentration of sodium saccharin was added to the stock diet of rats 1291.This iurther suggests that internal post-ingestion signals are capable of stahilizine caloric intake in exnerimental animals. It is eenerally bell'eved that humans are less adept in this capability and do not dependently make precise adjustments to maintain caloric balance. This calls into question the use of animals as a model of human eating hehavior. However, it should be recognized that, often, experiments have not been designed to reflect the choices available to humans in the modern world. I t has been shown that animals can be induced to overeat by the sensory properties of food alone under appropriate experimental conditions. When rats are offered successive chances of flavor or simultaneouslv presented with a varietv of flavors during a meal, food intakeis higher than when rats are offered a single flavor (30, 31). LeMagnen (30) used "odor-labelled diets" to show specific satiation effects of food stimuli at the peripheral level (Fig. 2). During a 32-day control period, rats received a daily 2-hr meal. On successive days, the diet presented was flavored by any one of four odor additives (citral, eucalyptol, benzyl acetate, or hemaldehyde). Then, during the same type of test meals, the four different diets were presented either successively for 30 min each or as one flavored diet during the entire meal as described for the control period. Under these circumstances, the successive changes of flavors in the course of a meal stimulatted food intake by 70%. Although these studies were short-term, they are more representative of human dietary conditions, in which several
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Figure 2. Satiation effects of flavor stirnull. I. Average f w d intake during the conbol w i d . 11. Average fwd intake in meals wM1 either successive or constant flavored samples. Flavws additives are citral (A), eucalypt01 (8). benzyl acetate (C). and benzaldehyde (D) (from (34).
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foods are served simultaneously. Moreover, feeding rats a varietv of sunermarket snack foods in a cafeteria-tvne set-un produees obkity (32) and is believed to be a r e l i s l e model of dietarv obesitv in humans. since humans also tend to eain weight ;hen offired a varied diet of palatable conventional foods (33. . . 34).. Rolls and colleaeues (35) . . have termed this overeating phenomenon "flavor- or sensory-specific satiety." In human studies, they found that the pleasantness rating of a specific flavor decreases during ingestion, while the pleasantness rating of other flavors remains the same. Thus, after a person is satiated with the flavor of one food, his motivation to eat foods of other flavors remains hieh, - . creatina-a potential . for overeating. Despite the results reported above, i t is premature to conclude that the flavor variety presented during cafeteria feeding studies (32) is solely responsible for the observed obesity. The sensory properties of supermarket foods are confounded by dietary composition factors such as high fat content. Subsequentlong-term studies should be undertaken to determine the contribution of flavors to byperphagia and obesity under conditions of controlled nutrient composition. If it is found that flavor itself contributes to dietary obesity, this would sneeest stimulation of eating bv the chemical senses under cir&mstances other than die& deficiency or emergency. I t could also he assumed that the mechanism for reeulatin-z food intake developed evolutionarily in deficiency si&ationi The availability of surplus nutrients thus produces a new circumstance for which a protective mechanism is lacking.
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Exocrine Secretions of the Gastrointestinal Tract and Digestion The role of oral stimulation in initiating secretory responses along the gastrointestinal tract has been investigated since the early studies by Pavlov (5). Taste, smell, sight of food, and anticipation of feedina all are to transfer sensorv signals t o auton"mw nerve centers which initiate digestivejuice secretions; this is termed the "cephalic phase" c:ltiJ or, according to Pavlov, "psychic e f f e c t s . ' ~ ~ a l i v a ~ o uist ~the u t first in ase; quence of exocrine secretions which occur along the gastrointestinal tract soon after food intake stimulates oral receptors. The term "cephalic phase" is usually used to describe reinonses such as eastric and nancreatic secretions stimulated "~ by receptors a t the oral level.'~ensationof ingested food also occurs at receotors located in the stomach and the intestine. usually leading to even more digestive juice secretions. ~ b e s e phases of secretion, which occur subsequent to ingestion, are the gastric and intestinal (36). To ascertain whether the chemical senses ~ . l .a avrole in initiating digestive secrt:tions, two fnctnrs should he considered. First. the eficct of stimulus ndatahilitv. or hedonic level. un secretory process initiation ghould be explored. ~econdly,the imnortance of cephalic-nhase stimulation. relative to the gastric and intestinal phases, in producing specific secretions should he determined. The extent to which food palatability contributes to saliva secretion has not been established. The major stimuli of salivation were found to be dry, solid foods, sour foods (37),and some odors with strong irritant properties which reflexively stimulate salivary secretion (38).Increased salivary responses to ~ a l a t a h l efoods have been renorted (39). but these results can be criticized on the basis t i a t olfacto;; stimulation was permitted, possibly allowing secretory responses to be initiated reflexively by odors. During a recent study, the anticipatory salivary flow was measured in response to the sight of several foods that varied in texture, composition, and acceptability (40). Salivary volume was found not to be related to anticipated palatability, but rather to the physical and chemical properties of the foods. The sight of f d s commonly perceived to be tangy or spicy resulted in the greatest salivary
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volume. Salivary secretion can be induced during conditioning and may accordingly be classified as a cephalic response. However, initiation of gastric and pancreatic secretions denends exclusivelv on intact vaei. whereas salivaw secretion does not, indicaGng different s%mulatory mechanisms. Cephalic phase stimulation of gastric and pancreatic secretions can be studied during sham feeding experiments in which ingested food is diverted to the exterior after swallowing and before reaching the stomach through an esophageal fistula (7).T o studv cephalic phase stimulation of eastric secretion &humans, mbdifiedsham feeding technique was used in which the subjects chew and expectorate food after contact with the oral cavity has been established (41). The gastric secretory response is mediated entirely by the vagus nerve (5), and in the dog, it appears within 5 min followingsham feeding. It can he produced during a pavlovian conditioning procedure (42). The cephalic phase of gastric acid secretion appears to have physiological significance; i t has been proposed that when all phases (cephalic, gastric, and intestinal) of secretion are in simultaneous operation in man, the cephalic phase is resnonsihle for one-third of the total amount of eastric secre'tion (41). Very little information is availabie on the ouantitative effect of food nalatahilitv or hedonic aualitv during the cephalic phase of gastric secretion. ~avlovreported that does that nreferred flesh to bread also secreted more gastric juice in response to sham fwding with flesh than with hread (51. the crmclusion that . . Other studies haw suonorted .. higher levels of gastric secretion are produced when more appealing gustatory and anticipatory cephalic phase stimuli are available (43). However, because the hedonic quality of the food was not used as a variable during previous studies, no direct evidence is available. Pancreatic exocrine secretion is also composed of cephalic, gastric, and intestinal phases (44). The ability of sham feeding to stimulate specific pancreatic digestive enzymes and also bicarhonilte o h p u t wis demonstrated in men-(451and dori (71. The physiological pathway by which the cephalic phnw . . itimulatis pancreatic exocrine~outputappears 6 vary among species. The mechanism seems to operate either through dirkct vagal stimulation of the (presumably theroute in man (41)), vagal stimulation of gastrin release from the pyloric antrum of the stomach, which mediates the action upon the pancreas (as opposed in dogs (7)),or through indirect stimulation due to the movement of eastric contents released cepbalically into the duodenum, which stimulates the intestinal nhase of uancreatic secretion. Since most of the dieestive " enzymes are secreted from the exocrine pancreas, we initiated studies to investieate the role of taste and ~alatabilitvin the cephalic phase orpancreatic exocrine output (46,4?). Dogs were prepared with gastric and duodenal fistulas, permitting continuous drainage of gastric and intestinal contents during experiments as well as exposing the main pancreatic duct for direct cannulation. Our experiments indicated that both pancreatic flow and digestive enzyme output can be affected by the nature of the taste stimuli. When coupled with swallowing, palatable taste stimuli exert a greater effect than do unpalatable stimuli. We concluded that palatability is relevant to the cephalic phase of pancreatic exocrine output. Our subsequent studies (28,48) were designed to explore whether diet palatability could play a role in digestive efficiency or food utilization through changes in cephalic phase stimulation during long-term nutritional study. We attempted to determine whether feeding rats unpalatable diets could reduce digestive efficiency due to possible interference with the cephalic phase of digestion. The results indicated that feeding the unpalatable diet resulted in a temporary reduction in feed efficiency (weight gain per gram of food consumed). However, this was found to be a secondary effect due to the reduction in food intake. In a nitrogen-balance study, no elevation of fecal nitrogen was seen in rats fed the unpalatable diet, suggesting no reduction in digestive efficiency. Rather,
a
higher levels of urinary nitrogen were found in rats fed the unpalatable diet compared to controls, demonstrating that D a r t of the ineested arotein was used for enerev rather than ;or anabolic ~ o c e s s ~most s , probahly due to thFreduced food intake. Moreover, analyses of digestive enzyme activity in the pancreas and along the intestinal tract (48) revealed that changes in enzymatic activity produced by feeding unpalatable diets were related to changes in food intake, rather than to specific effects produced by the unpalatability per se. One may therefore conclude that the unpalatable diets had no direct effect on either digestibility or on food utilization of rats under normal feeding conditions. The normal surplus level of digestive enzvme in the small intestine (49) and the low magiitude of the cephalic phase of pancreatic digestive enzyme output compared to other phases of secretion (7) may explain the lack of effect of the unpalatable diet on digestibility. Our results do not, however, preclude the possibility that the cephalic phase of t h e exocrine pancreasmay have nutritional relevance under specific circumstances when the digestive enzyme content becomes a limiting factor for digestion, e.g., in the clinic.
Conclusions
Taste and smell provide chemical information that is relevant to ingestion, digestion, and metabolism. The response of these physiological systems can be chemical specific. The chemical senses may play different roles in regulating diet during nutrient deficiency and during nutrient surulus situations. Literature Cited (I1 Lepkomky.Samual,in "The Chemical Sensesand Nutrition: (Editors Kare, M. R., and Maller, 0.1. Academic Press, New York. 1977. p. 413. 121 Riehter.C. P..Amar J.Physio1, 115,155(1936). 13) Seott,E. M.,andQuint,E.. J . Nurr.,32.113119461. I41 Rogers, Q. R, and Harper, A. E., J. Comp Physioi. Psycho!., 72.66 (19701. (51 Pavlw,lvan P.,"The Workof UleDigertiveGlands:' (trsns.Thompson. W.T.],GliNin, London. 1902. (61 Konturek, S. J., Kwieeien, N., Obtulowicz. W., Mikos. E., Sito, E., Oleksy, J., and Papiela, T., Gut,20,875 (19781. (7) Ploshaw, R. M.,Cnk,A. R.,andGrmsman,M. I.,Gostroenlerology,50.171 (1966). 181 Hommel,H.,Fischer,U., Retzlaff, K.,snd Knafler, H.,Diobetaioyio,8,111 119721. I91 D e w , J. A., Maller, 0..and Tomer, R.. J . Comp. Physiol. Psycho!., 81,496 (19731. (101 Desor, J. A.. Msller. 0.. and A n d r e w K.. J. Comp. Phyaiol. Psyrhul., 89. 966
Endocrine Responses ~~~~,
Studies have demonstrated that suecific tastes or the smell and sight of food can lead to a rapidrelease of insulin (8.50, 51). In dogs, sham feeding of glucose or plain tap water was able to increase the plasma immunoreactive insulin level (8). Topical anesthesia of the oral mucosa abolished the effect (52).In rats, gustatory stimulation by glucose, though not by sodium chloride, could elicit preabsorptive insulin release (51). These differential effects occurred even though both stimuli were presented a t appealing levels. Furthermore, solutions shown to be aversive resulted in no nreahsorative insulin release, and the insulin released by thk preferrid g l u c o s e s t i ~ u l u j could be abolished bv..uairine the alurose taste with LiCl illness. These results sueeest that. as for aancreatic exocrine secretion, palatability and experience are relevant factors in the cephalic phase of insulin release. The hyperglycemic hormone glucagon and the pancreatic polypeptide hormone are also released hv the cephalic mechanism (53.54).However. as for the exocrine pancreas, the postabsorptive effects of the food are quantitatively more significant than preabsorptive stimuli in the overall secretion of these hormones. Yet it is hypothesized that the early cephalic insulin release may have a relevant physiulogical:nutritional role. Even though only a small amount of insulin is released b y cephalic stimulation, it is released very early, before or during initiation of the ingestive events by the sight, smell, and taste of food (55,56)and thus may stimulnte subsequent eating. Insulin administration can lead t increased f i x d intake (57)and can cause an immediate hunger for sweetness (58).It has been hypothesized that the initial insulin release may decrease glucose availability and therebv increase huneer (56).Furthermore. even though an animaimay he satiateh by a i v e n food, sampling a difcrent food could initiate a new sequence of insulin release, which in turn would stimulate further ingestion. Should this hypothesis be correct, it may explain the physiological basis for the effect of flavor variety on intake. Indeed, rats displaying the highest degree of preabsorptive insulin release also ate more than animals showing a lower response (59).Moreover, it has been reported that preabsorptive insulin release was higher in obese human subjects than in normal weight subjects following exposure to the sight and smell of grilling steaks (55, 60). It was further suggested that the magnitude of the cephalic insulin response might he due, to a certain degree, to an index of a p p m t e However, more expermental data are needed in order t o \ a l l d a t e the a h v e hyputhes~sconcerning the role of preabsorptive insulin releasein dietary obesity
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~ a y & ~ G r o sW., s , &d walker, J. W., Brit. J. Erp. Pvlhol. 27,297 119461. Naim,M.,Ksrc.M. R.,and 1ngle.D.E.. J. Nut,., 107, 1652 119771. Rozin, Paul, in "Appetissnd Fmd Intake:' (Editors: Silverstone, T I . Dshlem Konferenzen. Berlin. 1976.p 285. Beauchamp, Gary K., and Msller. Owen, in "The Chemical Senses and Nutrition:' (Editors: Kare, M. R., and Maller, O.).AeademicPres~,New York, 1977, p. 291. Maskowitz, H. R.. Kumraish, V.. Shsrma, K. N., J a m b , H. L., and Sharma, S. D..
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Q"irnro 10" 11171~m1.1
(19) Mo&owitr, H. R., Kumraiah, V., Sharma, K. N., Jacobs, H. L.. and Sharma, S. D.. Physiol. Behou., 16,471 (19761. (201 London, R. M., Snowdon, C. T., and Smithans, J. M., Physioi. Behou.. 22. 1149 11979) ,... .,. (211 Gs1ef.B. G.,Jr,snd C1ark.M. M., J. Comp. Phyaid Psyehal.,78,220 119721. (22) Epstein, A., and Teitelbaum, P., J . Comp. Physiol Psycho;., 55,753 (1962). (231 J0rdan.H. H., J. Comp Physibl. Psychol., 68,498 (19691. ~ , i i C h e m i i I S e n ~ ~Nutritioi."(Edit~m: ~d 124) Naim, Michadand Karp, M ~ r l ~ y R "The Ksre, M. R., and Maller, O.),Academic Press, New York, 1977, p. 145. (251 Kmtz,C. M.,Levibky, D.A.,andLustick, S.,Physiol. Behou.,20,665, (19781. (261 Gentile,R.L.,Physioi. Behou,5,31111970). 1271 Kratz,C.M.,and Levitsky,D. A..Phy~iol.Beha". 21,851 (19781. 1281 Naim. M.. Brand. J. G..Kare, M. R, Ksufmann, N. A.. and Kratz. C. M., Physioi. B~hou..25,609(19801. (29) Kenney, J . J.,snd Collier,R., J . N u t r 106,388 118761. 1301 LeMagnen. Jac~ues,in "Handbwk of Physiology, Alimentary Canal: Sec. 6, Val. I, (Edilor C d e . C. F.1, American Physiolagicsl Society. Washington, DC. 1967, p. 11
(311 Treit,D.,Speteh,M. L..andDeuuch, J. A.,Physiol. Behou.,30,207 11983). (321 SElsfani, A , and Springer, D., Phyaiol. Beha"., 17, 461 (1976). (33) ~ I l sR. , J., Rowe, E. A , Rolls. E. T.. K i n w n , B., Megson,A., and Gunsry, R, Physiol. Behau., 26,215 (19811. (34) Porikm, K. P.. Hesser,M.F.,and Van1tsllie.T. B.,Physiol. Behal.,m,293 (1982). 1351 Rolls. E. T..Rolls. B. J..andRowe.E.A..Phvsiol. Rehou..30. 185 119831.
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(411 A i ~ h ~ l d ~C. o nT., . W B I S ~ .J. H., Cnper, K . A . , F d d ~ ~...~dFordtran, , J. S.,J Clrn.
1551 Rudin, Judith, in "Recent Advances in O k i t y Re8carch:Vol. 2, iEdilor Bray. G.), Newmsn, London, 1978, p. 75. 156) Louis~Sylvestre,J., snd LeMagnen. J.. Neumsri. Rehov RPU. (Suppl. I), 4. 43 ,,om, ,.""",. (571 Hoebol, G. R.,and Teitelbsum, P., J. Camp. Phy8iol. Psychol., 61,189 (19661. (581 Dsvir,J. D., and k i n e , M . W.,Psychol. Rsv.84.379 (1977). 1591 Berfhord,H. R.,Bereite~.D.A.,Trimble,E.R..Siegel.E.G..and Jeanrenaud.B..Diohelologio,20.393 (19811. (601 Simtrom. L., Gsrrellick, G., Krolkievski. M., and Luyckx, A , Melobolirm, 29. 901
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