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TO: r / ` May 2~~ 1983 G/Ii4Jt'f'g. - W. T. Hoyt FROM: Leonard S. Zahn SUBJECT: Federation of Amerfcan~Societies for Experimentali Biology, annual meeting Chicago, April 1i0-15, 1983 Lt was a typical FASEB meeting• more than 6 500 pre- a form that could be recognized. The usual format prevailed -- 1'ots of bits and'ipieces of information that are the buil'ding, blocks for progress in research. Of course, since submiissions to this meeting are not subject to screening, much of what was offered could be consideredlof little consequence. No major sci. entific discoveries were announced, at least in `' V sentations, at least thrice that number of scientists, and concurrent sessions spread so widely apart that peoplie were forced to scurry continually to hear papers of their choi~ce. l Taxis did a marvelous business. In the mass were several' dozen papers and posters directly or indirectlly related to smoking or to tobacco constituents; a few dealt wilth the behavioral aspects, especially in regard to nicotine effects. the mee ing. • BULI WELL was a featured speaker at a ses sion on tumor promotion. PETER M. HOWLEY received the Warner- Lambert/Parke-Davis Award'(and $3,000) from~the American Asso- ciation of Pathologists (AAP) which is given annually to an i'ndividual! under age 40 for meritorious research in experimental pathology. C. BARRY PIERCE received the Rous-Whipple Award from the AAP; this honors a pathologist over age 5&who carries on the tradi'tion of research achievement exemplified by Drs. Peyton Rous and:Ceorge H. Whipple, Nbbel Laureates. None of the tobacco papers attracted any press notice, so far as is known. There were few writers present and only one Chicago newspaper bothereIito send a reporter (and his stories were mostly, based on releases available in the press room). ~ Three Scientific Advisory Board members were honored during The highlights: 1. "Assessment of PIas.ase'-imduced structural and functional changes in sheep" -- H. SUSSKIND, Upton, N.Y. (a co-author was AARON JANOFF). emnh~_va which is producing findings he said are probably anal- ~"~• o, .. ~P eve op ~n an s co eagues are ng a s eep mo e uss or ~ #f /b& RkL iSIwT CC:WDHI 'i/6iC ffY-W'84' RFG ~ SCS RCH S17 Ac:c+,c[c- P7 t~ ~~~ y~' w• lit0,, ' . 1YL drv (I~ ' , ii d l ki d hi' ll h d l f S d ~ ` jevnard A ~ -_ (a,L/R(/(~,:~GS VUBYiC.BEUTiONSCOUNSEL SOftat2$jR4 _ 13 LINCOLN ROAD • P.O. 0OX 223 -GREAT NECK, N.Y. 11022' •(51E)482-5715

2. C agous to humans. He d'escribediexperiments in whi~ch elastase was instilled into the right lungs of 12 sheep to induce lesions; the left lungs served as controls. Lung perfusion, ventilation and volume were measured wilth the use of radioactive materials Ctechnetium, krypton and xenon) ~and the findings were analiyzed by computer. The animals were sacrificed four weeks after elastase instiLlation and the lungs: were examined. ti ". A.reduction in perfusion was found to correlate signifi~- cantly with increasing ellastase dose. The reduction also cor- " related'with increasing,structural damage in lung tissue. c. Susskind said the computer analysis and the imaging technique were effective in detecting,lung damage in the animals. 2. "Transient elevation of oxidized alpha-l-protease imhib- itor (Pilin hamsters with elastase-induced emphysema" EDITH LEVINE, St. Louis. This poster described the inhibitory activity of Pi, which normally protects against elastase destruction of lung tissue. By the fourthiday after instillation of the elastase, serum iinhibi- tion of elastase is decreased. Tihis occurs several' days after profound leukocytosis and at a time when the macrophages (',in lavaged lung fluid) have reached their peak. Thvs, the least inhibitionifollows the most acute injury patterniin the lung and coincides with what may be a more chronic inflammation pattern. Onder certain conditions Cthe poster said), such as in rats exposed to cigarette smoke or iin human smokers, the Pi apparently circulates as an oxid'izedimixture. It's suspected that the de- creased effect of Pi against ellastase (measured'.at days 4' and 5 of the experiment) is associated with an increase in the oxidized fraction and that as muchlas 20%' of the circulating Pi is oxi- dized. This finding may help explain the progressive lung,de- struction in elastase-induced'emphysema and the apparent absence of elastol'ytic activity. / CAROLYN MARLOW Louisville (su ~ { , pported'by Kentucky Tobacco and -Health Research Dnstiltute)''~,~,_ f'. ,.Pretreatment with three kinds of alcohol -- ethanoli, n- `,~, fi ^ butanol and t-butanoli -- appeared to protect mice from the carcinogenic effects of NNN, according to data offeredin thi ~fJs , poster presentation. Localization of the radioactive NNN inisal- ~kur o9~ ivary duct and bronchial epi,thelium and in both periportal and' ~ yl;central areas of the liver was reduced by pretreatment with ethanol and~, to a greater extent, with n-butanol. Pretreatment S' ff` did not inhibit accumulation in nasal, and esophageal tilssue. T-butanol at the higher dose (1g/kg) almost completely abolished the localization in bronchial epith~elium. The reduction ini 3. "Inhibition by alcohols ofthe localization of (i14:C)- ~ nitrosonornicotine (NNN) in epithelial tissues:of the mouse"

` .' 3', C photometric density was dose-related~. Pretreatment with allyl alcohol had'ilittle effect in inhibiting accumuLation of NNN in any site. Since t-butanol, onia volume basis, has about half the potency of ethanol iniinhibiting localization in bronchial epithelium, there may be other compounds that are even more potent. Propyl, butyl and~amyl alcohols are present in fermented beverages in different proportions. Also, al'cohols are present in certain types of cigarettes (e.g., menthol, a secondary alcohol) and in foods (e.g., retinol):. Inhibition of NNN'locaLization in the liver and bronchial ana saLivary duct epithelium only suggest that tumor incidence will be reduced inithese sites. Chronic exposure experiments are neeeded to see if this in fact the case. It's possible that inhibition of NNN in these three sites may result in an increased~ incidence of tumor formationiin ot`her sites. Most epidemiologic stud'ies have not separated the effects of different levels of alcohol on the incidence of cancer and defined'levelis of smoking,. One study (~SCHOTTENFELD:et al) had data from which one can calculate a reduction in standardized mortality ratios (SMR),from 12.6 to 5.3 with high alcohol con- sumption in low tobacco users. With high tobacco exposure, the reduction in SMR', from cancer with high alcohol consumption was evenimore significant, 26.7 to,1,7.5. However, there"s no evidence at present that permits a conoliusion as to the effect of alcohol on the incidence of lung cancer in smokers. 4. "Mucus hypersecreti',on in cigarette smoking dogs" f~Jw ~ ~ MALCOLM KING, Montreal. h IM{ 7° ~ na lL~' ` This was a praliminary report of a Larger study i~nvolivin a SV ' number of other scier.tists (inot iideitt' fied). It dealt with measurement of mucus secretion in 10dult bea 1e dogs wholwere ~(~~7'r( tracheostomized. After a four-month perio , six of the dogs were ~"1'J~Ptr exposed to a 35 cc bolus of smoke from an unfiltered 70 mm~ ~',!' y+~ _ cigarettes (:20, mg tar, 1.2 mg nicotine) each 20 seconds. The '~ `t e remaining four animalis served as controls. Q1 ~ s~fr-~ Each of the exposed'animals smoked 101cigarettes daily in 21 ~r Fw~`~ hours, 5 days a week. Two dogs were exposed for 6 months and 4 months. for 10 There was extensive mucus secretion in nearly all the smoking dogs, but the pattern varied in individual animaLs. Some of the dogs were hyposecretive at first. One animal had little hypersecretion during the 10-month,exposure period. Galactose content of the mucus fell in each smoking dog along with a decrease in elasticity. The dogs were killed at the en~d of the experiment and lungs are now being examined histologically. Dl ~ N

4. 5. °Inhibition of platelet adenosinediphosphate ('ADP') and serotonin release by carbon monoxide (COJ'" -- A. MANSOURI, Little Rock, AR. This poster presentation noted'that an increased incidence of atherosclerosis in smokers has been well documented and that smokers have enhanced pliatellet aggregation. This enhancement, whi'lcti results in the rellease of a large number of bioliogically active substances, has been proposed as a possible cause of damage to vessel wall endothelial cells. Mansouri has reported (in 1982) that, contrary to previous findings, platelet aggregatiion ils decreased~in the presence of cigarette smoke because of its C0 content.That aggregation and the release reaction may occur simulitaneously doesn't mean they are necessarily linked. His current research involves platelet reLease reaction in platelets"from smokers and nonsmokers in the presence and absence of CO. The release of serotonin and ADP was significantly decreased~ in the presence of CO. Platelets exposed to CO were found'to reliease signifi'cantly less serotonin when ADP or epinephrine was used an aggregating,agent. Wheniarachidonic acid'was used, there was noidifference i'n serotonin release iin CO1. These functions also were decreased iniplatelets from smokers. The release of serotonin was decreased in platelets from smokers compared to nonsmokers except when arachidonic acid:was used. ADP release was also inhibited~in platel'ets from smokers. Serotonin uptake was decreased iin smokers. To see whether CO was the prime factor in cigarette smoke that caused the decrease, the release reaction was measured in the presence of various concentrations of nicotine. Nicotine had ~ no effect on rotonin~reIease. Ther o good correlationibe- w lood carbox hemo lobin ~C0 ' nd the release reac- tion. is urprising ecause e COHb level in a smoker '.'.depends on the time of smoking and blood withdrawal, whereas platelet abnormalities persist for at least several hours.) Though platelet aggregation and the release reaction are general'ly decreased in the presence of CO and in cigarette smokers, they may not reflect the situation.that exists in the intact host. Atherosclerosis in smokers probably is the result of a combination of interacting factors for which no single in viltro experiment can give a clear understanding. 6. "Self-administration of nicotine by microinfusion into' the lateral hypothalamus of rats." -- EDGAR'T. IWAMOTiO, Lexington, (Tobacco and HealthiResearch Institut'e). Experiments with rats suggest that the lateral hypothalamus is aniarea in the brain closely involved inithe rewarding,effects of nicotine because the animals will self-administer nicotine dfrectly into this site. This ils the first time'any laboratory has reported suchian effect of nicotine after direct adminis-

/ C / r Y~..r" .~ S &,h"'` 1'`Y rr~"' , bP, , 5. o,-f- I ,f- tr ,~ ~ ~'' ` r,'` V Gr-~ b,r- I tration into the brain, Iwamoto claimed. ~ ~45 r . o tr, I (I In the test, rats were trained to press a bar for food~. Can- nulas were implanted~into their right lateral hypothalamus. On UPL' A Ninety minutes before each session, suspects drank either a placebo solution or got a dose of methadone that was either half, the same as or twice that of their regular dose. drug-free treatment. The high dose of methadone resulted in a two-fold increase in the number of cigarettes smoked'withiplacebo. A similar increase was found in the number of puffs and the inter-puff i'nterval. The number of puffs per cigarette and~the mean inter-puff interval showed no significant change as a function of n fromianxiety as well as other feelings perceived as pleasurable 1 y , rs~ p - . experimental days,, no food was given; instead, the animaLs got anicotine solution or a pliacebo. Rats on nicotine gave themselves Jf_J far more injections than did rats on the pliacebo. Iwamoto said the experiment was undertaken in the hypothesisV Ir-L~~ that people smoke because they find it rewarding or reinforcing. ~.td° ~ s Further, it was thought there are areas in the brain that, whenI Q~1o)~. stimulated b nicotine elicit elevation of mood and/or relief by the individual,. Results of the experiment imp1 that eo 'Ue smoke for the rewar ing,effec's o nicotine and eontinue to smoke rd'er t~ UULII.l-UC'i'CLC1V111}'LLIC L-CWdf'UJ. lL - '- - . ' - A-') novi' e goo effects or benefits to some eo le. The key to the ~~ ~f1 smoking pro iem, then, is to devise ways to remove the 'bad,' deleterious effects of smoking from tobacco." S SlL ~ The data make it possiblie to begin to'develop'a nicotine substitute that has all the rewarding properties of nicotine but which is devoid'of "bad," cardiovascular effects, Iwamoto said. His methodology can be used to screen potential nicotine-like agents and~determine their degree of inducing reward without interference from other brain sites. "Thus, in the future, tobacco users may be able to'enjoy just the beneficial effects of smoking,without the deleterilous effects that nicotine now causes. 7. "Dose-dependent effects of inethadone administration human ci'garette smoking" -- L/ D. CHAIiT, Baltimore. I .~i„ P, k sr4.-p on 4A e ause ciigare te smok ng is usually associated with other ~3 e WG drugs(e.g., alicohol, drugs of abuse), and because there's evi- dence that opiate systems may be involved in, smoking, a study was done of the effects of methadone on,cigarett'e smoking. Subjects were five men on methadone maintenance because of drug,addiction. They were isolated for 2 hours a day, five days a week, in a room where they couLd read or watch television; they smoked their regular brands of cigarettes. I G

6. \ .~; ' The higher dose of methadone also produced a higher rating of pleasure with smoking. Chait commented that it would be interesting to see if the findings couldibe duplicated inisubjects without a history of drug abuse. I ' 8. °EEG power spectral effects of intravenous nicotine administration in humans"'-- SCOTT LUCAS,, Baltimore (National Institut of D Abuse)' I t ~~ An/ e rug O . At, Pel- l 11 Eight healthy men with a:history of drug abuse had ele"c /- C trod'es attached for EEG readings while being given intravenous injections for 10 seconds of nicotine (or a placebo) in doses of 0.75 mg, 1.5 mg, or 3.0 mg. R'espiratory rate, heart rate and muscle tone were monitored for 10:minutes. 21 . The nicotine caused~a d'osd-related decrease in total EEG power. There was a dose-related increase in heart rate that was pretty much gone 2 minutes after nicotine admi~nistration. As for heart rate, there was an increase at the two liow,est doses that .contined for 10 minutes;. The high nicotine dose resulted in a; decreased heart rate that lasted for about six minutes. The subjects reported feelings of euphoria that were related to dose. However, three of them, upon being iinjected'~, felt "bad" for 10-1i5 seconds before euphoria set in. 9. "Plasma catecholamine levels in smokers and nonsmokers after psychological stress" -- A.A. WICKISER, Omaha, NE. i Catecholamine levels, as an indicator of stress, were :measurediin 43 men (30 smokers,, 13'nonsmokers) during three stress conditions: pu!blic speaking before all the subjects, memorizing and relating three jokes and competing for a cash prize according to the vote of the group. Baseline epilnephrine (E) and norepinephrine (NE) levels were determined at an earlier sessioni. E and NE were measured 30, minutes after the subjects were seated but before they were informed of what was coming. Measurements were then taken three minutes after each subject spoke. Pre-stress E and NE levels did'~not change from baseline readings for smokers and nonsmokers. Stress E!levels were signif- icantly increased over baseline for smokers and nonsmokers. Stress:NE levels increased only for nonsmokers. Pre-stress NE levels in smokers were high and'did'not change during the stress conditions. 10. "Lntimal smooth muscle cells as a source for atherosclerotic lesions" -- WILBUR'A. THOMAS, Albany, NY. Smooth muscle cells are present from birthisingliy or in, small masses -- intimal cell masses (ICM)-- in the arterial i~ Cv w ,d*- k-Fh

7. i~ntima of vi'~rtually all species. It's not known whence the ICM originate. The situation is exceedingly complex. The cell population in an artery i~s very heterogeneous with a composition that is changing as the resulit of celli births and~cell deaths and in-out migration from the vessell walli. Experiments were done with a model system involving the abdominali aorta of swine, some of which were subjiect to a balloon treatment to create arterial damage while others were fed either an atherogenic of nonatherogenic diet. Swine fed an atherogenic diet from 8 weeks to one year were found to have extensive atherosclerosis. The lesions seemed to. arise from ICM. In swine fed a normal' mash diet, the imtimal cells did not ,, increase significantly ininumbe.p during the first year, but medial' cells increased several-fold. Further studies showed that the intimal cells doubled in number every 80 days. ,4 Tf S M)` ~~ ~~ w h t v` v~Y /~et~e C / ~J 11." Herpes virus (HN) nd atherosclerotic lesions in ~ a humans" -- . RETT, Seattle (EARL BENDITT'was a co-author)'. ~ Experiments with specimens of aortic tissue taken fror patients undergoing coronary bypass surgery indicate that HV may be present in the thoracic artery of patients with signif- icant atherosclerotic disease, Barrett said. There's no idea of the incidence of this particular kind'~of HV infection. Evidence for the presence of the virus was found in 113 of more than 1!001specimens. Some specimens positive for the virus seemed to:be in early stag,es of atherogenesis. There was no evidence of other kinds of viruses such as cytomegalovirus or Epsteiin-Barr virus. Barrett hypothesize&that the virus could injure epi!thel:ial cells lini~ng the arteries or could:cause genetic injury to in- dividual smooth muscle cellis in the vessels. 12. "Antinociceptive action of nicotine and its methiodide derivatives in mice and rats" -- BILLY R. MARTIN, Richmond, Va. Animal tests with methodides indicate that nicotine probably attains its effects through a central mechanism, rather than peripherally. This seemed to be the major coneIusion~foIlowing~ tail-flick experiments with synthetic methiodides formvlatedifn Martin's laboratory. - Nicoti'.ne pyrrolidilne methiodide produced a:great deal of seizure activity, probably through a central nervous system effect. Nicotine pyrid'i~ne methiodide and nicotine bis methodiode were inactive at high doses and produced almost no antinociceptive activity, and no seizures (nociceptive - causing,

8. , or reacting, to pain). Methiodiides penetrate the brain at very low levels compared to nicotine, according to the findings of tests in which both substances were injiected into rats. 13. "Effects of ascorbic acid supplementation on lungg function and physical endurance in smoking and nonsmoking male subjects" -- THERESA HEFFERAN, Blacksburg, Va. This study, reported i~n a poster presentation, covered the effect of ascorbic acid (vitamin C) supplementation of 1000 mg daily on l'ung function and athletic performance of 10 nonsmoking and'7 smoking males between the ages of 21 and 40 years. At the outset, the smokers had significantly lower levels of pulmonary function and treadtnill workl'oad', and they tended'to have lower plasma levels of vitamin C'and abso u e oxygen con- s,~sumpt~ion than dild nonsmokers. The smokers also had higher ~Sµ,s post-exercise heart rates. ~_~ After vitaminiC supplementation, it was found there was no x L. change in smokers ai7d nonsmokers in pre-and post-exercise heart rates, blood pressure, treadmilL workload and various pulmonary function measurements. 1lI` ~ 14. "Ascorbic aciid status of smoking and nonsmoking adolescent females" -- SUSAN B. MOSSHOLDER, Auburn, AL. This poster presentation dealit wilth a study of the vitamin C status of 11 smoking and 58 nonsmoking females aged 14 and 16 years, eachiof whom had'ibeen smoking about 9 cigarettes dailly for approximateLy2y' years. Significant differences were found iin dietary intake, plasma and leukocyte concentrations of vitamin C for both groups. Smokers had reduced dietary intakes and plasma viltamin C lievels in comparison to nonsmokers but higher leukocyte values of the vitamin than nonsmokers. Dietary intake and plasma values of vitamin C indicate a low ascorbic acid status for smokers but a well-nourished status for nonsmokers. However, both groups had leukocyte ascorbalte con- centrations characteristic of a well-nourfshed status. Iimpailred' absorption of vitamin C was postulated to be responsible for de- creased plasma levels in smokers, but the mechanism is unknown. 15. "Chronic cigarette smoke exposure alters (,114C')arachi- donic acid'('AA) metabolism iin platelets, lungs and aortas from rats" -- W'.C. LUBAWY, Lexington (Tobacco and Health Research Institute). " ' A study was done of the effect of chronic smoke exposure on the conversion of AA to prostacyclin and thromboxane in rats platelets, lungs and aortas. (:Prostacyclin, a piostaglandin, is a

9. C potent vasodilator and inhibi~tor of pliateliet aggregation; throm- boxane, another prostaglandin, has the opposite effect.)i A change iin the balance of these two has been 1!inked with certain types of cardiovascular disease. The animals had daily 10-minute exposures to fresh cigarette smoke (Kentucky 2R1 cigarettes) 5 times a week for 10 weeks be- fore being sacrificed. Examination of the tissues disclosed , evidence of an imbalance between prostacyclin and thromboxane.fti '- ~~`^'` ~ , 16. CARL BECKER, New York, had two poster presentations dealing with ~ familiar subject: tobacco glycoorotein (TGP). One A l°r rL poster dealt withithe mitogenic effect of TGP on various ce11s, f1 ~ from mice and concluded that TGP maght be a B-cell mitogen (a substance'that causes ceIli division and transformation). Is •ensitivitv to it. The thrust was that TGP elicits an exclusive Immunoglobullin E (IgE) response in mice. In a private discussion, Becker told me that "if some people are like these mice, they'11 be very anaphylaotic,, very reactive to the stuff (TGP) because they don't have the antibodies to block the action." The other poster said TGP was rich in rutin or rutim-li'ke ~~,~,,~ substances and that half of norffiaL humans (both smokers and ~dgf- nonsmokers) have been found to show an immediate skin hyRer- PS "The histolo ic spectrum of lun tumors observed after*, ' 17 g g . exposure to polycyclic hydrocarbons" - WILLIAM BLAIR Chicago , . ~ ir, , • This poster presentation reported that lung tumors of L' S different histologic types were induced in more than 90% of So.&• ~`, femalie Sprague-Dawley rats after iintratracheal instillation of ~~ Lu/''(Y benzo(a)pyrene (5aP) and~ferric oxide. Histologic types and percentage distribution with,BaP' were: squamous ce1i1 cancer 60%; ~^ adenocarcinoma 13%; smallcell carcinoma 19%; large cell pl"" ~bn-t carcinoma 5%; mucoepidermoid carcinoma 1%; and sarcoma 2%a Nq.~~ tumors were induced with ferric oxide. The tumors metastasized and eventuall y killed the hosts.~ Each of the induced tumor types was transplantable into syngeneicfr, hosts. w MISCELLANEOUS ITEMS: Because the severity of atherosclerosis in~premenopausal women is less than that in men, a:study was done to see whether the difference was due to reduced numbers of precursor lesions in the women. GARTH AUST'IiN, Atlanta, reported that an autopsy study of aortas from 39 males and 37, females ranging in age from 9-30 years found'precursor lesions were similar in number iniboth sexes. The reduced severity of atherosclerosis in premenopausal women may be due primarily to slower progression of the precursor lesions in men rather the women having fewer of.such lesions. -0-

1o. k. J.D. FOLTS, Madison, WI, who may be remembered as the scientist who has gained publiicity for claiming smoking ex- acerbates the development of platelet thrombi, at lieast inidogs whose coronary arteries he stenosed wilth plastic cylinders, gave with the usual techniques (snares, balloons, etc.Y. a paper in which he sought to answer what he said was a question often asked: Why i'is,he the only one who has reported inducing thrombi with the use of the cylinders? Without mentioning his smoking work, Folts said acute,platelet thrombi and reductions in coronary blood flow occur with the cylinders because they cause a •:,longer lesion and provide more surface area for damage and sub- sequent thrombus formation. He's been unable to induce thrombi PETER ROWLEY,,Louisville, reported finding that after an for long perio s o me. ~-- ,1 , t d i i' initial breaking-in period of several weeks, nicotine could be given to experimentali animals in drinking water up to a concen- tration of 100 micrograms/liter with no decrease in fluid intake or weight gain as compared to controls. He claimed to have de- veloped a technique to maintain laboratory animals on nicotine ~r x 1~ ( ~) I .,~• ~V r.y. '(7b H.,~:. MEIER,, Balitimore, with several others, iincluding CTRrYW grantee*C.G. COCHRANE, reported that lung, Hagemanifactor cTeaving ,h r en~~zyme (LHFA), previously described by them as being released from ~,h human lung fragments, seems to be an elastase present in mast 1~"'' cells and basophils. (Mast cells are iintegral parts of connective e~ tissue, basophils are circulating cells.) Indications ar(! that LHFA may play, aniimportant role in inflammatory processes in thes liung. ~~ -0- INGRID SCHRAUFSTATTER, La Jolla, CA,, (with Cochrane as a :co-author) reported experiments in which pulmonary injury was induced in rabbits by instil'lati'on of chemicals. Dnjury stim- ulated neutrophils to release oxidants and proteolytic enzymes into the surrounding,tissue to result in "exhaustion" of the defense systems agaiinst oxidants. -0~ The effect of naloxone on the "pleasure"' of'cigarette smoking was studied in human subjects by ROGER PALMER, Miami, FL. Naloxone was injectedlinto the subjects after they'd abstained from smoking for six hours. Following injection, the subjects were permitted to smoke as they wished and graded their "pleasure" response inicomparison to air drawn through a drinking straw. The results, Palmer said, were consistent with the con- clusion that opiate receptors and endorphins are involved i~n the -11 oc)h c,o ft~