Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 1966 Some effects of lysergic acid diethylamide on visual discrimination in pigeons Daniel I. Becker Yale University Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Recommended Citation Becker, Daniel I., "Some effects of lysergic acid diethylamide on visual discrimination in pigeons" (1966). Yale Medicine Thesis Digital Library. 2386. http://elischolar.library.yale.edu/ymtdl/2386 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. YALE MEDICAL LIBRARY Digitized by the Internet Archive in 2017 with funding from The National Endowment for the Humanities and the Arcadia Fund https://archive.org/details/someeffectsoflysOObeck i’f SOME EFFECTS OF LYSERGIC ACID DIETHYLAMIDE ON VISUAL DISCRIMINATION IN PIGEONS by DANIEL 1. BECKER A Thesis Presented to the Faculty and the Officers of the Yale University School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Medicine September 1966 Department of Psychiatry Yale University School of Medicine ACKNOWLEDGEMENTS The author gratefully acknowledges his debt to Dr. James B. Appel and Dr, Daniel X, Freedman. Dr. Appel's continual contributions of instruction, guidance and encouragement were invaluable. The experiments were conducted under his supervision In the Psychopharmacology Laboratory, Departments of Psychiatry and Pharmacology. His influence is evident throughout this work. Dr, Freedman provided a perspective and many helpful suggestions which greatly furthered these investigations. Thanks also are due to Dr, Malcolm Bowers, whose generous aid and careful editing were most welcome. This research was supported in part by USPHS Research Grants MH-03363, MH-5942-14 and MH-5942-15 from the National Institute of Mental Health. ft’itJ*!^' a^p.9^vl,i94Kfe; -iidw ‘“lit '* ■ V.' ''.'A’ ,XCfi% ''^'^ ^“'^0 ^ '-'^''C,.; l,^»i^''f«ti^eid tabnu'' '^a . V: 'i^'v - ,/' ‘ .'iti'i'-’’*^^' * ''lifiMflMi' ^'" B*®’”' ' 1, , ' Ji rT4-V^.i!f^ ■ TABLE OF CONTENTS Page List of Tables iv List of Figures v Introduction and Literature Review 1 Method Subjects 6 Apparatus 7 Behavioral Procedure 10 Pharmacological Procedure 10 Results Accuracy of Performance 11 Experiment I 11 Experiment II 14 Experiment III 18 The Experiments Combined 18 Dose-Response Data 18 Food Consumption 25 Discussion 30 Summary 36 References 37 diuW*.J btlio fiwsirto’uboitn'I IV TABLES Table 1. Average Per Cent Errors (Total Incorrect Responses Divided by Total Responses) - Experiment I Table 2. Average Per Cent Errors, NaCi and 20 pg LSD/kg, All Experiments Table 3. Total Number of Pauses, All Experiments, by LSD Dose Table A, Median Time of Pause Start and Median Pause Duration, All Experiments, by LSD Dose 2tn^fT»h»qx3 llA ,g9l\<3ej qq CK bno iDoH v, .S «icloT ' Li Uf‘" ' ' x-i. .. .• V-*' ." ’,,• ...^L ' I' L .^lli I I A _ • . .. #*!'* <« . * t A A I >• t ^ A.A . - . « t ^ ' ''iM*.. A ,noI^07ua «k^up^ ni&ji&9M brto'-^feiiT <9o(b»M > aldoT V'M-'-i 1 IL AfJ’’ i ’ .« b J 1. Fa) I I di'.ot3 (32i. ' .. -■mh- ,>.:■; 1?,^ V'>7>l ■ ■; ' 'i:■■•.■■■»'K* ■' ■ ' ' i ' > 4 '.'. -L. -flfiS .'<■ ' 'ri; ‘ ^ ])<.w.i' iV: ' ■'.'I ■'.■■■ JjBj, m.;.;.kmk i fL '"V’V'J'r'. ** * ■ ,4 ,■ :• lilVt^ 1... vK'■' ■■'A'f'<"'^ '7 , V * '■ .■'> .'4''" .i '‘"V Ai,y'flifi I,' 'v5f*-''i\‘4*|fV^'‘^f V FIGURES Figure 1. Flicker Control Apparatus Figure 2. Experiment h Per Cent Errors by LSD Dose and Flicker Frequency, Average of Six Birds Figure 3. Experiment II: Per Cent Errors by Flicker Frequency, Average of Three Saline Sessions for Each of the Six Birds Figure 4. Experiment II: Per Cent Errors, Saline and Three LSD Doses, Shown for Each Bird, Average of Six Different Flicker Frequencies Figure 5. Experiment II: Per Cent Errors, Saline and Three LSD Doses, Shown for Each Flicker Frequency, Average of Six Birds Figure 6. Experiment III: Per Cent Errors by LSD Dose and Flicker Frequency, Average of Six Birds Figure 7. Dose-Response Measures: Rate of Response/LSD and Total Time/LSD ^ Rate of Response/NaCI Total Time/NaCi' By LSD Dose for Each Experiment, Average of Six Birds Figure 8. Median Pause Duration by LSD Dose, Shown for Each Experiment, Average of Six Birds Figure 9. Frequency of Pauses Occurring Per 2-Minute Time Interval After Start of Experiment, Shown for Each Experiment and LSD Dose Figure 10. Experiment II: Weight Gain Per Session by LSD Dose, Average of Six Birds, Six Sessions Per Bird at Each Drug Dose and Eighteen Sessions Per Bird with Saline Ifl'’"^;"v' '\, , ' .vNr^WVp»,i3,OZi yd fiior3;fn«'!).yT#^';il.tA<WG''b»aK3 '■'^.S'WiwBf^ ' > ,;;. eb'-M'S ,xf:-5. }p ,i»j80tav^.i,. ','^1 «9B^*^igkvA,.^yDn»upt»-i^ •»©>f3M'^ yd ^<>*^3.^ ,,0'f *" ' •. ^' '"■' ■ ' ^ " ’■ '* ■ 4)'': ■AffEra;>'|-'■ »““ - — ■-'VaftirIT • bf»D-*’•- ©niloS-■■••'■r 1^- 8wii3,■- -J--^ ,/-T -- 'iU-".•'- -.T-w^.-- —••■^■ oi-. ■^,;,.,l\a '■VJ_.:i« - r ift.>}:>il3 tnsnsifHO x?? ?3 vgo^svA, tliJlfB H3P3 10^ ' ,„■'''' H.,,';, -4 ■ . '*"' 'I-:..C^^h. <'?^-^ . - uIy"^, nwcric ,e»epCl Q?J o^irif bno»ni|p2 v^'’oii3 Vrtt>»cnhbqx3 t/^C ©tuol^ft' f . , ,, <fbilfi xi2 ^o ©goiavA ,yonauf>di3 rfooS io1 ■• "1^- ''M . ,|1 '»■ * k’J #, V. „ ^ \ y till iiWiiKpa- '’.6_etuaii' ■i. ■'(f)' ^ i. ,'"* 'Hi ii- ibi!3 Mf2 }o 0^itn«vA , ’.,,,-^ =' Jbno q?-!\s;n°q^^ ,J'EiteM Mno<,»a-<.»Q A «U811 ^ f\r,.,)' f>r u,. 'i; «bil8 x»2 1o ©goievA ^tn©fini‘:9qx3 Hat)3 lo^ pcpO Q2J yfl jT^ tnejnl 19^x3 Hpd3 nwod2 ,9?o0 02J yd nmt4?'.uC}^»K<.o^‘oofb»M ,8'^'Migjn '< T ib>l8 xlZ W ©poi©vA ’ V I' .' mil A lo7is>lrtr,.9rrtf7 jatunfMrS g'^hiupii^O ii<wweiM lo : X»nPopoi=t .9 (]U! 1-. ■. « »?ciCI C12J bno 1oomIl,9qx3 HaoB ml nwodS .^lnismii^qxl lo ti^ ’i'ji 1^ ■ .'*■' . ■#;,' '1 '.>.’jfi' • - I •■': i "i'' 'I 'lo ©qdisvA »9i»Q Q2J yd noimS i9*i n{oO»k-friQ*«iW rll meOTlieiqkS .Of 01UB‘^ f mW- 'i- wLr,r«*w»^'%^3 bno ©soQ guiO doo3 tD bil8 isS 4j<K>(«a?2 xii? cib,:»l€ xl2 .,r«^ii ___. nwimm f 4’, (, wo j 1 oZ' dtf w-b nA/"iiiA.''Wk»hj#® Zjt" k:i>r’AA' 1. INTRODUCTION Experimental evidence, while often seemingly confused and contradictory, tends to confirm clinical reports that visual processes are uniquely sensitive to compounds of the general structure of lysergic acid diethylamide (LSD). Such agents have been called "hallucinogenic" or "psychotomimetic," perhaps because of bizarre visual sensations which sometimes occur in man following the ingestion of micro-quantities of drug. Neurological investigations generally report an increase in the electrical activity of visual systems with LSD, but neither the exact character nor the precise location of these effects is clear. Current knowledge of the neurophysiological effects of LSD relating to vision will be briefly outlined, beginning with the retina and progressing centrally. Jacobson and Gestring (1959) found that in 40% of cats given 50 micrograms per kilogram of d-LSD, spontaneous electrical potentials could be recorded from the eyeball which were abolished when the optic nerve was sectioned. Apter and Pfeiffer (1957) found that cats given 100 pg LSD/kg also demonstrated this effect. Schwartz and Cheney (1965a), also using cats, state that intra-peritoneal injec¬ tions of high doses of LSD produce a retinal state analogous to stimulation with light flickering at high frequencies. Apter and Pfeiffer conclude that LSD does not produce hallucinations in humans with section of the optic nerve. Jacobson and Gestring believe that the effects of LSD upon visual perception are central in origin, but Ostfeld (1961) feels that LSD in humans (75-100 pg) leads to hypoxic or toxic retinal changes. In a later paper. Krill, Alpert and Ostfeld (1963) found that LSD could indeed o1 ?{«vhu-ri?»-2 >(ji9upmu‘ s>id ?*5reie>jKnv:| iau'Siv of :''huc (Cil'J; .^fbtfntefxj^lo-fb h.iso Immisii^ «:nt }q j*bmKK:|mo;;;» ..f*', ''.V »«w«;ayi#d 2qDfbf»q 3jt^,jT,imofoHDV(2q’*' to rtsrOc'l avcx? «fn»QO fti>J'ti«5QrTi srit g''i-iwr.>!lvf+ nr O' nj luooo etniif ?T»ox»fl 'i , .^ihh !o 2'«-fittrtDtjp«'aiokm 3o >- .'Y lDohf:>r»^ i) aril n> *‘ao'>ioni no ■<''ioq:r»i yMuisn^^ 9fic®-j-q >ofl *»s*t:)oiorio foay& •tsrllte"’ 'tvd blw Iv-f^v yiivMoo <DoiQok'i.2yTfqoiu-on s4t 31•.'>(>.• •; rn-sin;") ^'*0^1 ^ ■aigrti ttorfr'^c^ srit Hflw qrttnrtlooc' ..bciilifiio xTlshu ad M;W '■••d/iv of -i •^■■: J lo yilor! no'. bno ooif»'’ imoiQO'tofnvor r'wio i;fro ofO' td ^'orn bnuol tyii'f Vv"» 0 Kna no«ionol moi^ hfirb‘,r^;n acf blun-a elolfnetoq IrnT-iilosir. .-t,';>t>nc-^fioq2 ,0?J-d motgolM laq (, onp intqA bbnoJlDaj 6vtt>n "dt nskHvv ha'tii’fJedo daid v ISwcisytjj orlt' ?tdf bftiDilmomeb osk* q/ O. i gif OOJ novio .'‘-o ■‘odt'':,nuot (K^t) itj^fb^ - -odjnt losnotiioq-oifnl ^odt alol? . qnl.iv.! o>‘ o ^ Iw.' ffiowHoc IHgi'l driw noi .tdotTiit? O'* ^u,0'J*.Hjnb a*oT2 loniJ ^i -ityubcto Gc'J kj j«job"*4pni k> .?>»»obi>pcrd dgtH r> f'.'. 1 .,„.;' tit' nJ t.'xo'tors'ouilr'ri •"’nt/boiri fon etWsb QEJ !t‘dj >V .ifd bno t*?tqA nrit forlt avai'Ud sjohtfsO brro noedoooL .csvi^o bifqo a'-if (lo.