THE CONTRIBUTION OF OROPHARYNGEAL SENSATIONS TOHYPOTHALAMIC HYPERPHAGIA

BY DENNIS McGINTY,* ALAN N . EPSTEIN AND PHILIP TEITELBAUMDepartments of Biology and Psychology, University of Pennsylvania .

Finickiness accompanies the overeating andobesity that are produced by ventromedialhypothalamic lesions. Decreases in the palata-bility of the food that do not affect the normalrat will depress feeding in the hyperphagic rat(Kennedy, 1950), and can even render the animalaphagic (Teitelbaum, 1955 ; Corbit & Stellar,1964) . Improvements in the taste and texture ofthe diet exaggerate food intake in both thedynamic (Corbit & Stellar, 1964) and the static(Teitelbaum, 1955) phases of the phenomenonand elevate the level of obesity in the static phase(Corbit & Stellar, 1964) . Clearly, the vigour ofthe hyperphagia and the level of the obesityreached are functions of the palatability of thediet.

To what extent does the phenomenon of hypo-thalamic hyperphagia depend on palatability?Will the rat with ventromedial hypothalamiclesions overeat and become obese if it cannottaste or smell its food? The question can beanswered with a technique described by Epstein(1960). Rats will eat food that does not passthrough the mouth and pharynx .They feed them-selves by pressing a bar for the delivery of foodinto their own stomachs through a chronicgastric tube. Normal animals feed themselvesfor months with this method and regulate foodintake with precision (Epstein & Teitelbaum,1962b). The following is a report of hypothalamichyperphagia in rats feeding themselves in thismanner .

MethodsSubjects

Intragastric feeding was studied in eight adultfemale rats of the Sherman albino strain . Theanimals weighed between 250 and 290 g . atthe beginning of the experiment . In six of theanimals, ventromedial hypothalamic lesionswere made prior to the beginning of trainingfor intragastric feeding. All gained at least 75 g .before being introduced to the experiment . Theseventh and eighth animals were fitted withchronic ventromedial hypothalamic electrodes

*Now at the Brain Research Institute. UCLA .

413

before training and the lesions were made afterintragastric feeding was well established . Hypo-thalamic placements were at stereotaxic co-ordinates A :6, RL :0 .75, Down : 9 .0-9 .5 mm.from the surface of the cortex . In all cases, thesagittal sinus served as the reference midline .In the six animals made hyperphagic beforetraining, bilateral lesions were made with anichrome anode (1 mA ., d .c . for 30 seconds) .In the seventh and eighth animals a pair ofinsulated platinum electrodes was fixed to theskull (Hoebel, 1964) and the lesions were madesubsequently under light ether anaesthesia(3 mA., d.c. for 40 seconds) .

DietsTwo types of liquid diet were employed. The

first was an enriched eggnog (Williams &Teitelbaum, 1959) that contains 1 .55 k .cal. perml. This diet contains insoluble material andtends to clog the intragastric tubing . It wasreplaced during the experiment by a completelysoluble diet for the rat supplied by General Bio-chemicals Incorporated (Chagrin Falls, Ohio)as their soluble diet No . 116 EC. It is a lessexpensive version of the Greenstein L-aminoacid diet (Greenstein, Winitz, Birnbaum & Otey,1957). It contains casein hydrolysate instead ofthe amino acids, sucrose instead of glucose, andthe vitamins, minerals, "Tween" emulsifier,and essential fatty acids as described by theoriginal authors . It is a 50 per cent. solutionthat contains 2 k .cal. per ml .

Intragastric FeedingThe essential elements of the intragastric

feeding technique are a chronic gastric tube,a diet delivery-system controlled by a bar avail-able to the animal, and automatic programmingand recording equipment which permits unin-terrupted study of the animal's behaviour . Thetechnique has been described in detail elsewhere(Epstein & Teitelbaum, 1962 a and b) .

The rats were first trained to press the bar toobtain liquid diet for oral consumption . Thenumber of bar presses required for each deliverywas increased by steps to six . The initiation of

4 1 4

intragastric self' feeding was accomplished byswitching the diet supply lint from the foodcup to the inlet of the gastric tube . The next timethe animal pressed the bar six times, 2 .5-3 .0 ml .of liquid food was injected (0 . 1 ml ./sec .) directlyinto the stomach instead of into the cup . Inone animal (IGM-1), the method was modifiedto give the rat complete control of the size aswell as the frequency of its meals. The pump wasactivated by depression of the bar and remainedactive as long as the bar was held down . Therate of delivery was fixed at 3 .4 ml. per 10seconds . A recording circuit was devised thattranslated the duration of bar press into verticalexcursions of a cumulative pen . Water wasavailable at all times from a graduated cylinderfitted with a drinking spout .

Test for RegulationRegulation was tested during intragastric

feeding in five animals by diluting the diet tohalf its concentration with tap water. Regulationwas achieved if the animal maintained a constantdaily food intake, i .e ., doubled the volume of itsintake on days of 50 per cent . dilution andhalved its volume of intake upon return to fullstrength diet.

Oral IncentiveIn three animals, a small amount of solution

was delivered into the cup in the cage simultan-eously with the intragastric load . In two thisincentive was the eggnog diet, and in one it was0 .1 per cent . sodium saccharin solution (w/vin water) . In all three animals the volume of theincentive was one-ninth the volume of the con-current load .

ResultsFive of the eight animals were hyperphagic

ANIMAL BEHAVIOUR . XIII, 4

while feeding themselves without taste and smell .In the three others the addition of oral in-centives was necessary to maintain bar-pressingduring intragastric feeding. The results for thefive rats that did not require oral incentives aresummarized in Table I. In two rats (IGM-1and IGM-7), hyperphagia was produced afterintragastric feeding was established . The otherswere hyperphagic before they fed themselvesintragastrically . Table I shows the animal's bodyweight at the time intragastric feeding began, themaximum weight reached after hypothalamiclesions, average daily food intake and weightgain during intragastric hyperphagia (dynamicphase only), and the total number of days ofintragastric feeding . All animals overate andgained weight steadily to moderate levels ofobesity .

The detailed data of one rat (IGM-1) areshown in Fig. 1 . In this animal both meal sizeand frequency were self-controlled. The pump ranas long as the bar was held down . Note first thata sustained hyperphagia leading to more than200 g. increase in body weight was produced bymedial hypothalamic lesions while the animalfed itself by injecting food into its own stomach .A first set of lesions on day 9 in the figure pro-duced only three days of overeating. On day 34a second set produced the sustained phenomen-on. After each pair of lesions, the hyperphagiawas expressed initially as an increase in meal sizeresulting in a clear doubling of daily food intake .

In all five of the animals in Table I, food intakewas regulated in the face of abrupt changes inthe concentration of the diet . This is shown ondays 37 to 43 of Fig. 1 . After 50 per cent . dilutionof the diet, indicated by the division of the histo-grams into filled and open halves, the volume ofliquid consumed doubled within three days . Theadjustment to dilution is made precisely but

Table I. Hypothalamic Hyperphagia and Weight Gain to Moderate Levels of Obesity in Rats Feeding themselves wit o tTaste or Smell.

*Mean values during dynamic phase,

Subject Initial

Maximumweight

weightI

I

Daily IG*food intake

Daily IG*weight gain

Total daysIG feeding

IGM-1 260

!

488 64 .2 5 .4 58

IGM-7 282

390 53 .7 4 .0 50

IGM-19 247

414

i 96 .5 7 .6 48

IGM-10 325

423I

55 .6 2 .7 73

IGM-25 295

348

I 42 .7 2 . 8 26

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Fig . 1 . IGM-1 : Hyperphagia and moderate obesity in a rat feeding itself without taste and smell .Body weight in grams, food intake in millilitres . QHCL indicates days ofadulteration ofthe diet with0 .03 per cent . quinine hydrochloride .

10

31

slowly (compare it with the adjustment made ondays 2 to 6 before lesions). This delay in adjust-ment to dilution was seen in all five rats . Theconverse adjustment to concentration was equal-ly precise and as rapid as in normal animals(Epstein & Teitelbaum, 1962b) .

All the animals that were hyperphagic beforeintragastric feeding was instituted decreasedtheir bar-pressing and food intake during thetransition from oral to intragastric feeding(see IGM-10, Fig. 7, Teitelbaum & Epstein,1963). The animals included in Table I (IGM-19,10, and 25) adjusted to the change by increasingtheir intake and became hyperphagic . The re-maining three animals became severely anorexic .These were the animals that required an oralincentive. All were vigorous hyperphagics wheneating by mouth. Bar-pressing and hyper-phagia were restored in these animals by the

45

58 99

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introduction of a small oral incentive (eggnogin two, 0 . 1 per cent . saccharin in one animal)delivered into a cup for oral ingestion concur-rently with the delivery of the food into thestomach .These phenomena are shown in Fig. 2. When

eating eggnog by mouth the animal is vigorouslyhyperphagic, consuming over 100 ml . per day .On transition to intragastric feeding, bar-press-ing and food intake drop immediately . On thefifth day the animal is aphagic . The introductionof saccharin (0 . 1 per cent. w/v) incentive restoresbar-pressing. Food intake rises to hyperphagiclevels, and once begun, the overeating and weightgain continue at a slower rate after the with-drawal of the incentive (days 14 to 30) . A secondand more sustained dynamic phase is produced byreintroducing the saccharin incentive (day 45 inFig. 2) when the animal's weight had stabilized

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4 16 ANIMAL BEHAVIOUR, XIII, 4

at 410 g. and food intake had fallen to non-hyperphagic levels. A higher level of obesity(480 g .) is quickly reached . With the oral in-centive (days 45 to 60) the animal ate 53 .3 ml ./day and gained 70 g. in 15 days. Without theincentive (days 14 to 30), the animal ate only41 .8 ml./day and gained only 40 g . It shouldbe noted that in this case the incentive is acompletely non-nutritive solution .

The two other rats that required oral incen-tives were the most obese animals studied at thetime intragastric feeding began (425 g . and484 g.) . Both animals ate less and lost weightwhen taste and smell were withdrawn . In both,hyperphagia and rapid weight gain returnedwhen the small oral incentive was added to theintragastric load .

DiscussionThese results show that high palatability of

the diet is not necessary for hypothalamichyperphagia. Rats overeat and become obesewhile feeding themselves foods that do not pass

DAYSFig. 2 . The addition of a saccharine incentive restores bar-pressing and hyperphagia (days 8 to 24), and prod-uces a second dynamic phase and a higher level of static obesity (days 45 to 60) in a rat that was vigorously hy-perphagic when eating by mouth .

through the oropharynx. The overeating cannotbe simply the result of exaggerated responsive-ness to the taste and smell of patalable foods .

However, taste and smell are potent ener-gizers of feeding in the normal and particularlyin the hyperphagic rat . Palatable diets havebeen shown to be essential for the onset ofhyperphagia, for maximum rates of food in-take and weight gain in the dynamic phase andfor maximum weight levels in the static phase(Corbit & Stellar, 1964) . The experiments re-ported here supplement these findings by show-ing that without the taste and smell of palatablediets the hyperphagic rat will not eat as vigor-ously. This is strikingly demonstrated by theexperiments shown in Fig. 2. The animal wasone of our maximal hyperphagics when pressinga bar to eat by mouth . It quickly stopped pressingand became aphagic when it could no longertaste or smell its food. But when a non-nutritivesweet-tasting incentive was offered with eachgastric load, the animal was once again moti-vated to overeat . These excessive reactions to

McGINTY et al. : OROPHARYNGEAL SENSATIONS AND HYPOTHALAMIC HYPERPHAGIA 4 17

taste and smell are additional demonstrationsof the finickiness of the hyperphagic rat, that isseen in both the dynamic (Graff & Stellar, 1962)and static (Teitelbaum, 1955) phases of thephenomenon .These experiments also show that as rats

become obese, high palatability becomes essentialfor sustained hyperphagia and maximum obesity .Our rats did not reach high levels of obesitywhen they could not taste or smell their food .When the obese level was reached the mereaddition of a small, sweet incentive restoredhyperphagia and weight gain . This is reminiscentof the increased oral food intake of obesehyperphagics when sugar is added to their diet(Teitelbaum, 1955) .Additional evidence for the importance of

palatability for sustaining hyperphagia in theobese rat comes from our finding that our mostobese hyperphagic rats did not overeat and lostweight when switched from oral to intragastricfeeding. Their body weight had apparentlyalready exceeded the level at which food intakein the absence of palatability is depressed byobesity . Hoebel and Teitelbaum (in Teitelbaum,1961) have already shown that obesity curbshypothalamic hyperphagia. They described a ratwhich was subjected to ventromedial hypo-thalamic lesions, after it had become obese asthe result of overeating in response to chronicinsulin hypoglycaemia. It did not display max-imum hyperphagia until it was deprived of foodand forced to lose more than 230 g . in weight .Obesity also depresses food intake in the neuro-logically normal rat. Cohn & Joseph (1962)have shown that rats, whose body weight hasbeen raised to twice the normal level by forcedfeeding, do not eat spontaneously for as long as16 days after the forced feeding have beenstopped. In the rat feeding itself intragastricallywithout the incentives of palatability, the depress-ing effect of obesity on food intake operates atlower weight levels .

The importance of taste and smell as energizersof feeding behaviour is further shown by theslow regulatory adjustments made by ourhyperphagic animals. In previous experimentsneurologically normal rats feeding themselvesintragastrically (Epstein & Teitelbaum, 1962b)and hyperphagic rats eating by mouth (Williams& Teitelbaum, 1959) increased food intake tochanges in dilution rapidly, usually within thefirst night of feeding after the change . In allanimals tested in the present experiment, intra-gastric food intake was doubled in response to

50 per cent, dilution of the diet, and food intakewas halved when full-strength diet was returned .But the adjustments to dilution were much de-layed. Food intake was never doubled duringthe first night and typically the regulation wasnot achieved until the third night of dilution .

These findings support the view that motiva-tion is essential for the regulation of food intake(Teitelbaum & Epstein, 1933) . The taste andsmell of food are powerful reinforcing stimulithat serve to motivate the behaviour involved infeeding. Normal animals, with adequate motiva-tion, can largely ignore taste and smell andregulate their food intake in the face of widevariations in palatability and dilution (Adolph,1947). But in animals with hypothalamic dam-age, where motivation is impaired, regulationwill be delayed or will not be achieved unlesshigh palatability is operating to motivate foodintake .

SummaryHypothalamic hyperphagia was studied in

rats that fed themselves food they could nottaste or smell. Overeating persisted in theabsence of oropharyngeal sensations . However,high levels of obesity were not reached . Theaddition of small oral incentives produced newbouts of overeating and rapid weight gain .Excessive responsiveness to highly palatablefoods is not the cause of hypothalamic hyper-phagia but oropharyngeal sensations determinethe rate and duration of the overeating and areessential for maximum levels of obesity .

AcknowledgementsSupported by grants USPHS NB-03469 to

Alan N. Epstein and NSF G-24386 to PhilipTeitelbaum . The authors are grateful to Mr .Robert Glassman who conducted the experi-ments with IGM-1, and to Miss Sandra Lee whoprepared the figures .

REFERENCESAdolph, E. F . (1947) . Urges to eat and drink in rats .

Amer. J. Physiol., 151, 110-125 .Cohn, C. & Joseph, D . (1962). Influence of body weight

and body fat on appetite of "normal" lean andobese rats . Yale J. Biol . Med., 34, 595-607 .

Corbit, J. & Stellar, E . (1964) . Palatability, food intake,and obesity in normal and hyperphagic rats . J.comp. physiol. Psychol., 58, 63-67 .

Epstein, A . N. (1960) . Water intake without the act ofdrinking . Science, 131, 497-498.

Epstein, A . N. & Teitelbaum, P. (1962a) . A watertightswivel joint permitting chronic injection intomoving animals. J. app!. Phvsiol., 17, 171-172,

418

ANIMAL BEHAVIOUR, XIII, 4

Epstein, A . N . & Teitelbaum, P. (1962b) . Regulation offood intake in the absence of taste, smell, and otheroropharyngeal sensations. J. romp. physio!.,Psycho!., 55, 753-759.

Graff, H . & Stellar, E . (1962). Hyperphagia, obesity, andfinickiness . J. comp . physio!. Psycho!., 55, 418-424 .

Greenstein, J . P., Birnbaum, S . M., Winitz, M . & Otey,M. C. (1957). Quantitative nutritional studies withwater-soluble, chemically defined diets . Arch .Biochem. Biophys., 72, 396-456.

Hoebel, B. G. (1,964) . Electrode-cannulas for electricalor chemical treatment of multiple brain sites .Electroenceph . clin . Neurophysiol., 16, 399-402.

Kennedy, G. C. (1950) . The hypothalamic control offood intake in rats. Proc. roy. Soc ., B., 137,535-549 .

Teitelbaum, P . (1955) . Sensory control of hypothalamichyperphagia . J. comp . phvsiol. Psvclwl., 48, 156-163 .

Teitelbaum, P . (1961). Disturbances in feeding anddrinking behaviour after hypothalamic lesions .In Nebraska Symposium on Motivation, M . R.Jones, Ed . University of Nebraska Press, Lincoln .

Teitelbaum, P . & Epstein, A. N. (1963). The role oftaste and smell in the regulation of food and waterintake . In Olfaction and Taste, Y . Zotterman (Ed.).347-360. Pergamon Press, New York .

Williams, D. R . & Teitelbaum, P . (1959). Some observa-tions on the starvation resulting from lateralhypothalamic lesions . J. comp. physiol. Psycho!.,52, 458-465 .(Accepted for publication 27th July, 1965 ;

Ms. number : 585).