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I I I I I I I I I I I I I I I I I I Life Sciences, Vol. 38, pp. 997-1003 Pergamon Press Printed in the U.S.A. INCREASE OF CIRCULATING BETA-ENDORPHIN-LIKE IMMUNOREACTIVITY CORRELATES WITH THE CHANGE IN FEELING OF PLEASANTNESS AFTER RUNNING Johannes Wildmann+, A~nd Krugern, Matthias Sc~moleII, JUrgen Niemann , and Heinrich Matthaei +Max-Planck-Institut fur experimentelle Medizin, Forschungsstelle Matthaei, Gottingen Institut fur Sportwissenschaften, Georg-August-Universitat Gottingen (Received in final form December 19, 1985) Summary Twenty-one male regular long distance runners participated in two 10 km runs one week apart. Their 3-endorphin-like immunoreactivity (B-EIR) was assayed in plasma before and immediately after running. Mood was monitored by an adjective check list (Eigenschaftsworterliste, EWL) pre- and post-run. (i-EIR was significantly elevated post-run. Self-reliance and good mood scored higher after running. Both mood elevation and plasma (3-EIR increase showed a considerable individual variability but there was a significant correlation in the mean values of the two runs between individual 3-EIR increases (oR-EIR) and the changes of ratings in feeling of pleasantness (oFP). High o(3-EIR corresponded to positive mood change post-run. Introduction Activities such as exercise and running are followed by a variety of physiological responses which are mediated in part by the secretion of catecholamines and several peptide hormones. Plasma levels of ACTH and B-endorphin have been found to be elevated concomitantly (1), which in turn might be responsible for increases, in plasma cortisol and growth hormone as well as prolactin concentrations (2). On the other hand it could be clear- ly shown that long lasting physical exercise, for example long distance running, is followed by acute mood changes (3). Reduction of state anxiety and increased feeling of pleasantness turned out to be the most prominent changes (4). There have been successful attempts to utilize the anxiolytic and antidepressant effects of running in the treatment of moderately depressed patients (5). Severe anxiety states and depression belong to the most malevolent psychologic distress human beings can experience. The prevalence of anxiety in modern industrial populations is indica- ted by the high incidence of prescriptions for minor tranquilizers in western countries. It seems very worthwhile to devote attention to body own possibilities for regaining psychosomatic health and 0024-3205/86 $3.00 + .00 Copyright (c) 1986 Pergamon Press Ltd. I

I I I I I i I I I I I I I I I I I 998 Running and ?food Changes Vol. 38, No. 11, 1986 to learn more about the underlying mechanisms. The endorphins in particular have been suspected as playing a part in eliciting mood effects as well as being the cause of the anecdotically described phenomenon of the "runners high" (6). Some effects of running and exercise such as iltered pain perception and miosis are antagonized by naloxone (7, 8). After acute exercise, high doses of naloxone increased ventilation and catecholamine titers in plasma which indicates participation of endogenous opioids in the control of circulating catecholamines (9). Up to now, little experimental evidence could be provided that peripheral (3-endorphin plays a part in the emotional altera- tions mentioned. The failure of antagonzing the behavioral ef- fects of running using low doses of naloxone was considered an (l0~ment against the interference of endorphins in this respect This study attempts to show whether mood change and increase of plasma 3-EIR after long-distance running are correlated in each individuals. Subjects and Methods Twenty-one male volunteers all of them regular long distance runners for years participated in this study. They were healthy, on no medication and non-smokers. They all were used to running regularly at least once a week. For details see TABLE I Specifications and Performance of Volunteers Age Height Weight Average Years of running intensive distance running (years) (cm) (kg) per week (km) Mean 29,8 180 69,8 56,6 7,4 S. D. 10,7 4,7 5,7 35,9 7,6 range 18 - 62 170 - 185 60 - 78 10 - 115 0,5 - 33 In order to minimize accidental intrapersonal and situa- tional variabilities every participant completed two 10 km runs a week apart under equal conditions. For statistical evaluation average values from both runs were used. The participants were introduced to the intensions and procedures of the study and gave their informed consent. They answered a corresponding questionaire which revealed that every one of them was already experienced the psychogenic effects of running on their own. Fitness, enhancement of performance followed by the increase of psychic pleasantness were most frequently stated as motivation for running regularly. Reasons of catharsis, social aspects and competitive arguments were rated as less important. I

I I Vol. 38, No. 11, 1986 Running and Mood Changes 999 I TABLE II I 1 I Participants Motivation Score to Run Regularly Social Reasons 11 (pts), Catharsis 19, Fitness 29, Performance 26, Competition 8, Increase of pleasantness 22. Inquiry scale point system: strongly disagree 2 (pts), agree 1, undecided 0, disagree -1, strongly disagree -2. The scores represent the summarized valuations of all partici- pants. ~ Testing took place between 14.00 and 18.00 hr. The volun- teers were instructed to run 10 km, i. e. 25 laps on a 400 m all weather track, up to maximal aerobic capacity. Lap times were registered to plot individual speed variations. Mood was moni- ,.r tored using the EWL (Eigenschaftsworterliste) scale, an adjective ~ check list. EWL is a multidimensional method for describing the actual mood state. It was developed in 1961 and was validated by correlation with other adjective check lists (11). Mood is judged by agreement or rejection of 123 adjectives given by the test. ~ The items record 14 aspects of mood (activation, concentration, deactivation, tiredness, mental clouding, extraversion, introver- sion, self-confidence, elation, excitement, emotional sensivity, irritation, anxiety, depressive mood and thinking introversion) , which can be categorized into 6 fields. The field "feeling of pleasantness", includes the aspects self-confidence and elation, covering a total of 19 items. According to the authors of the EWL-list average ratings of the feeling of pleasantness have been ~ proved to be 8 - 10 items, indicating a"normal" mood. The EWL- questionaire, which defines state of mood, was answered three times: at rest at home, immediately prior running and 10 min after running. In addition, a trait personality test (FPI) (12) was completed at home. Blood samples were drawn by venipuncture ~ immediately before and 7 min after finishing the run and a third sample was taken 3 hr thereafter. Blood samples were collected in siliconized glassware placed ~ on ice containing EDTA-Na (9 ug/5 ml whole blood). After centrifugation (10', 00 C~ plasma samples were frozen and stored at - 350 C as a source of B-endorphin-RIA. Samples were thawed only once and assayed in duplicate. ~ R-endorp~hin RIA: For the determination of circulating R-endor- piin=Tike immunoreactivity (3-EIR) a commercially available assay kit (INC, Stillwater, USA) was used. It involves extraction of R-endorphin from plasma by anti-B-endorphin coated sepharose ~ particles. Incubation: 21 hr at 20 C. Phase separation is achieved by a second antibody method. An internal standard was run with the assay. The antibody used does not descriminate N-acetyl-B- endorphin, des-tyr-endorphin and a-endorphin. The assay showed r neglectible or no crossreactivity with B-lipotropin (< 5 %), L a-endorphin, y-endorphin, dynorphin, leu- and met-enkephalin, r.~ ACTH and others (none). The range of sensitivity was 0,5 - 80 p ~ mol/l plasma. The intraassay variation was < 10 %. OPb ~ Statistics: For every participant, the a-EIR increases (post ~ ~ - ~~ s ~ Cr~: ~ I

I I I I I I I I I I i ` ' _ ,i ~ ~ * ~ 1000 Running and Mood Changes Vol. 38, No. 11, 1986 run values minus resting values) and the differences (post minus pre run) in EWL ratings related to the feeling of pleasantness were averaged for the two runs. The Spearman rank coefficient of correlation was used to describe the connection between the increase of plasma (3-EIR and mood change after running. Results After running a distance of 10 km, which the participants completed in a mean time of 39 min 11 sec (SD + 5'13 "; range 33'44 "- 55'11" ) plasma 3-EIR was significantly increased (19.6 +_ 9.2 pmol/1) as compared to pre-run values (4.6 + 2.7 pmol/l P < 0.0001). This result is in accordance with earlier studies (13, 14, 15). Three hours after finishing the run, circulating 5-EIR concentrations were found to have returned to the range of starting (3.2 + 2.0 pmol/1). Considerable individual variations were observed as far as resting a-EIR and increase of t3-endorphin titers after running were concerned, indicated by high standard deviations. The test retest correlation of the two runs for (3-endorphin increase was significant at the 0.01 level which highly indicates that the intra-subject variability is consistant. TABLE III Individual Changes of Mood Score (4FP) and (3-EIR Levels (^3-EIR) i. e. Post-minus Pre-run Values Subjects IFP (items) 1./2. Run ~,Li-EIR (pmol/1) 1./2. Run 1 - 2 (- 4/ 0) 7 ( 6 / 8 ) 2 8 ( 8/ 8) 23 (21 /25 ) 3 13,5 ( 16/ 11) 26,5 (37 /16 ) 4 3 ( 0/ 6) 8,25 ( 1 /15,5) 5 0 ( 0/ 0) 14,75 (13 /16,5) 6 7 ( 4/ 10) 11 ( 9 /13 ) 7 5 ( 9/ 1) 16,75 ( 7 /26,5) 8 13 ( 14/ 12) 28 (22 /34 ) 9 0,5 ( 1/ 0) 17 (21,5/11,5) 10 - 3 (- 1/- 7) 7,25 (12 / 2,5) 11 - 2,5 (- 4/- 1) 16,5 (15 /18 ) 12 4 ( 4/ 4) 18,5 (16 /21 ) 13 11 ( 121 10) 28,75 (27 /30,5) 14 - 2 (- 1/- 3) 10 (10 /10 ) 15 1 ( 0/ 2) 12,75 ( 9 /16,5) 16 - 8,5 (- 8/- 9) 3,5 ( 4 / 3 ) 17 - 2 (- 4/ 0) 7,5 ( 7 / 8 ) 18 5 ( 8/ 2) 27,5 (34 /21 ) 19 2 ( 4/ 0) 23 (24 /22 ) 20 3,5 ( 2/ 5) 7,5 ( 1 /13 ) 21 1,5 ( 0/ 3) 5 ( 3,5/ 6,5) All values are means of 2 runs. Single values are given in ~ brackets. ~ ~ C= . ~ Cst 00 ~

I I I I I I I I I I I I I I I I Vol. 38, No. 11, 1986 Running and Mood Changes 1001 General feeling of pleasantness, which combines items of the EWL checklist related to self-confidence and elevated mood, scored higher post-run'as compared to pre-run. The mean increase of the two runs for all subjects tested was 2.79 + 5.54 from a total of 19 items. Again considerable individual differences were striking (see S. D.), therefore the increase did not reach sig- nificance. Item alterations (~IFP = post-run minus pre-run values) grouped under self-confidence and elevated mood and the cor- responding increase of plasma (i-EIR (af3-EIR = post-run minus pre- run titers) are given for every individual subject in Table III as mean values of the two runs. The Spearman rank coefficient of correlation rs fur mean Af3-EIR and mean oFP is 0.7377 (P < 0.001, Fig. 1). 0-1 Ln E 10 ~ .~ N N (D C C d O a 0 ~ 0 rn C ~ v • • • . L-10 0 15 30 A f3-endorphin IR (pmot / 1) FIG. 1 Graphic presentation of the correlation between Al3-EIR and oFP for each participant as means of 2 runs. Discussion Long distance running (10 km) is followed by an increase in 3-endorphin IR and changes in mood. Both parameters showed high, inheritant individual variations. In addition to individual pre- I

I I I I I I I I I I I 1002 Running and Mood Changes Vo1. 38, No. 11, 1986 dispositions, cognitive influences and esthetic sensations per- ceived during running may vary and influence chemical factors such as opioid peptides stimulated by long-distance running. There are no significant or obvious relations to performance, age, or years of intensive training as could be shown before (15). In this study a correlation between circulating !3-EIR in- crease and feeling of pleasantness could be clearly demonstrated for the first time. In an earlier investigation a similar corre- lation did not prove to be significant, partly because of the insufficient number of participants (16) as well as substancial inter-subject variability. Arguments against the involvement of endorphinergic system in mood elevation after running were put forward by Markoff and co-workers (10), because of their failure to antagonize these effects. However, these investigators may not have used a dose large enough to block endorphin activity, and they did not measure central or peripheral endorphin levels. On the other hand, at least three different types of opioid receptors were suggested by physiological studies (15), just as opioid receptor binding studies demonstrated the presence of multiple opioid receptors (16). Only the .:-receptor, which interacts with morphine-like drugs, is effectively blocked by naloxone (17). For antagonism of other ligands much higher naloxone concentrations are required. u-receptors seem to be related to analgesia and they mediate the formation of miosis. Behavioural and mood effects such as euphoria and mania are thought to be triggered by putative o-receptors. Reduction of pain sensitivity after running and exercise and its antagonism by the u-receptor antagonist naloxone is well documented (7, 20). Also u-receptor-linked development of miosis in humans after running was naloxone reversible (8). But in the light of these considerations, naloxone concentrations employed to antagonize mood changes (10) appear far too low to become operative on a-receptors. Also see Ref. 21 for more detailed comments on this study. No simple conclusion, may be drawn as to the relationship t between endorphinergic alterations and emotional elation a / consequence of the correlation between R-endorphin and mood; nor is it to be interpreted as a direct connection of these two facts. Moreover, up to now there is no clear evidence that peripheral ~, endorphins possess central actions or even whether they covary -/s with the activity of the central endorphinergic system. Long dis- tance runners constitute a unique population, therefore, results cannot be generalized to all subjects. The group studied had been running an average of 7 years and changes in peptide storage, ~ release and feedback might have occured over time. • As indicated by the motivation scores (see Table II), participants of this study could possibly represent a certain ` selected group of individuals, who are above average in their s ability to experience the psychogenic effects of running because of specific physiological preconditions which indirectly induce ~ them to run. ~ ~ All in all, general statements can only be made when possible ~ interactions of basicindividual psychological parameters have been ~ ~ . C) ~ ~ o

I I I I I I I I I I I I I I I I ol. 38, No. 11, 1986 Running and >iood Changes investigated. Acknowledgment 1003 The skillfull technical help of Mrs. W. Kopp is gratefully acknowledged. References 1. F. FRAIOLI, C. MORETTI, D. PAOLUCCI, E. ALICICCO, F. CRES- CENZI and G. FORTUNIO. Experientia 36 987-989 (1980). 2. Y. KATO, Y. JWASAKI, H. ABE, S. OHGO and H. IMURA. Proc Soc Exp Biol Med 158 431-436 (1976). 3. J.A. BLUMENTHTC; R.S. WILLIAMS, T.L. NEEDELS and A.G. WALLACE. Psychosom Med 44 529-536 (1982). 4. D.P. NOWLIS and N. GREENgERG. Percept Mot Skills 49 1001- 1002 (1980). 5. J.H. GREIST, M.H. KLEIN, R.R. EISCHENS, J. FARIS, A.S. GUR- MAN and W.P. MORGAN. Compr. Psychiatry 20 41-54 (1979). 6. C. PARTIN. JAMA 249 21 (1983). 7. R.J. HAIER, K. QUAT15 and J.C. MILLS. Psychiatry Res 5 231- 232 (1981). 8. M. ALLEN, J. THIERMAN and D. HAMILTON. Can J Appl Sport Sci 8 98-103 (1983). 9. A. GROSSMAN, P. BOULON, P. PRICE, P. DRURY, K. LAM, K.G.M.M. ALBERTI, T. TURNER, G.M. BESSER and J. SUTTON. Clin Sci 67 483-492 (1984). 10. 77A. MARKOFF, P. RYAN and T. YOUNG. Med Sci SPT 14 11-15 (1982). ` 11. W. JANKE and G. DEBUS. Eigenschaftswbrterliste (EWL), Verlag fUr Psychologie Dr. C.J. Hogrefe, Gottingen (1978). 12. J. FAHRENBERG, H. SELG and R. HAMPEL. Das Freiburger Per- sbnlichkeitsinventar (FPI). Verlag fiir Psychologie Dr. C.J. Hogrefe, Gottingen (1973). 13. J. DEARMAN and K.T. FRANCIS. J Sport Med 23 30-38 (1983). 14. W.M. BORTZ, P. ANGWIN, I.N. MEFFORD, M.R. BUARDER, N. NOYCE and J.D. BARCHES. N Engl J Med 305 466-467 (1981). 15. W.D. COLT, S.L. WARDLOW and A.C.-77ANTZ. Life Sci 28 1637- 1640 (1981). - 16. P.A. FARREL, W.K. GATES, M.G. MAKSUD and W.P. MORGAN. J Appl Physiol 52 1245-1249 (1982). 17. W.R. MARTIN, hG. EADES, J.A. THOMPSON, R.E. HUPPLER and P.E. GILBERT. J Pharmacol Exp Ther 197 517-532 (1976). 18. L.E. ROBSON, S.J. PATERSON and H.W. MTERLITZ. New York Plenum Press, Vol. 17 p 13-80 (1983). 19. K.J. CHANG and P. CUATRECASAS. J Biol Chem 254 2610-2618 (1979). . - 20. B.C. SHYN, S.A. ANDERSSON and P. THOREN. Life Sci 30 833- 840 (1982). 21. L.S. BERK and S.A. TAN. Med Sci SPT 14 V (1982). I