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»DRUG Media Research” (Arzneim.-Forsch. 6 , 359-364 )
Editio Cantor / Aulendorf i. Württ.
From the Institute of Pharmacology at the University of Bern; Director: Professor Dr. W. Wilhrandt
Tierpsyehologische methods that have been used for the investigation of drugs
Assoc. Dr. Peter N. Witt
From the Institute of Pharmacology at the University of Bern; Director: Professor Dr. W. Wilbrandt
Tierpsychologische methods that have been used for the exploration of Arzneimi en
By Assoc. Dr. Peter N. Witt
Often bring new methods of investigation, significant progress for a branch of science. . Thus, for example, the manometric measurement of tissue respiration in Warburg – multiplied apparatus in .wenigen years our knowledge of the cell metabolism. Conversely, whole groups of new substances can be found and applied already in therapy, without adequate pharmacological methods have been developed to their r ru- Fung and identification. The latter seems to me in some cases, the situation in the pharmacology of the central nervous system, where FHE phenothiazine derivatives, z. B. the Largactil-Megaphen (WZ.) Have become widespread in psychiatric iherapie without through much more than a has been working ‘Beit (Courvoisier et al. 1953)’ tried to create experimental animal documents for its rational application. It is the task of this essay to be, to-sam’menzustellen existing animal psychology methods to figure out how far, and how well you prepare already m use of medicines found telforsdiung Jiaben and thus inre routinely correct application.
The corresponding works are scattered in many magazines, and psychological journals predominate; the methods were still mainly used to klären.’Letzteres psydiologische issues is au A why daii the work carried out sometimes appear pharmacologically wrong us, too little material has been used for high or low doses or substances were tested, their effects is of no particular pharmacological interest. oo were taken into account in the present selection hardly work examining the effect of glandular disorders, malnutrition or Hirnresektio- NEN. At the appropriate places only the collating work to be mentioned. 1 vCfcíí * “
The compilation is not complete. Some of the magazines especially Russian and less common American journals, were not accessible to me / so that I could not systematically work through very old works often seemed no longer of topical interest. On the other hand, I believe that the cited studies give a good cross-section detail unimportant face indem’sie important and already much made use of methods briefly in greater numbers.
The summary of various works under a common title is often happened something by force. The investigators have the methods varying from case to case, have chosen different doses of substances and various types of application, various animals used for testing ^, so that the results can not be compared with one another without reservation. This may have been for the psychological issues of benefits, but makes in the pharmacological evaluation difficulties, because we are accustomed to asking here, which constantly reproducible effects produces a substance as opposed to another.
Many works have been made in order to clarify questions of human psychology, as: it affect stun the higher mental functions ?, or: Can Tetrqäthyl- ainmonium reduce the fear ?, or: Increases glutamic intelligence? And carried out with a lot of effort Studies have this question, at least for the reader, not settled satisfactorily. Even if such a question could be answered for rats; seems the transmission of the results to humans is far right. The functions actually audited are so unclear, or so many intertwined inseparably that the interpretation of the results is subjective.
The extensive pharmacological application that we would like to wish these methods seem to relate more to comparative studies of the effects of various substances. So you can examine the effect of a substance which has been tested on humans beieits with an animal method and compare this result with the test result of other substances that have been investigated in the same way. Same effects in animal studies are likely to comply with even the same effects in humans. In each chapter works are mentioned, where tested series of more than 100 chemically similar substances for their efficacy using animal psychological methods and useful for potency and specificity (few side symptoms) have been read out in a short time. Furthermore, antagonisms can be measured quantitatively. For such studies, often simple and zahjenmäßig evaluable methods seem ideal. So here show the most useful results when tested by many substances with the same methodology. Such an approach also requires no highly problematic assumptions about certain mental qualities in animals.
The title already restricts the number of methods to be discussed. Some methods in which one can argue whether it should be mentioned even animal psychology, I have not discussed; I will mention just a few more important such works. This includes testing the susceptibility to convulsions (Good-
■ ii a neo. Swinvard 1949 To be 1951 Wolf 1951 Kew’itz et al. HK & IW?
Hi ■ HK Page I
Pfeiffer et al 1952- u Häusler 1952. Volkmer u !: Win ter 1954; S.chaefer 1955 Nathan et al. 1955) and the registration of partly controlled mentally but physically anchored more processes such as breathing Blutäruck, appetite and so on-also the methods have found no mention of that as yet only once or twice found for testing drug-effects application, and therefore its pharmacological test have not filed.
Observation of the behavior
The first attempt to get to know the effect of an unknown substance is then made, dall is this an animal possible parenterally teach and then observed its behavior. Such monitoring may already mentioned as a method, or it can be brought into a more standardized form. The mouse treated with a certain low dose of morphine is suddenly up her tail; with – dog treated hashish begins to totter, biting into the air, staring into space. Such phenomena are used to read from different severe poisoning or the chronological sequence of poisoning stages. A method developed from it. For example, an attempt is made to capture the effect of scar coticums in intensity and duration by observing the occurrence of various Çtadien. The Städien may be laid down in advance exactly how Gross et al. (1955) it (the, WZ Dori-) have done on the dog in the investigation of the new sleeping pill a-phenyl-a-ethyl glutaric acid:
1. \ restlessness, increased movement, ataxia,
2. stronger ataxia,
3. rest, dozing,
4. Sleep well woken up,
5. sleep, hard to be woken,
6. anesthesia, by external stimuli not to be woken.
The authors write in the assessment of the method itself, that one always has to work with the same dog to get consistent values (and we may add: always with the same observers), or that when using multiple dogs a huge material must statistically evaluated in order to detect the average value of a far scattering population. It is a simple, no equipment requiring method that is the drawback ‘of a wide scattering of the obtained values and depends on the person of the experimenter. Examples of such studies are those from Riesser. Hadrossek (1930), See verse (1936b), Corns- weet (1938, 1939, 1941), Riesser (1938), Wal ton e, t al. (1938).
This method has – as far as they can be identified as such at all – even to important results in, out of drug discovery. L œWe (1944) z. B. used the 5 Stages of Dog tumble tests, to clean with its aid in 2600 tests on 150 dogs that derived from hemp hashish drug more and more of fiber, to which a tiny amount substance was isolated, which the unchanged effect throughout the drug gave the dog while the rest substance showed no significant effect more. This pure substance obtained was then Adams u. Al. (1941-42) will be identified as a tetrahydrocannabinol. The simple test has therefore made a significant contribution to the discovery of hashish active chemical compound.
^ .A, Further improvement consists in observing the animals in very specific situations, as Plant and Pierce (1928), See verse (1936 a, 1948), Wrappers (1944) did. or in the bedroom and in the Weckmitteln
Measurement of onset of sleep, ‘duration and would run H mh S tor u. Pick 1926 Barlow et al. IW Chicken 1936 Pfeiffer et al. 1939 House chi 1 d 1939 Wynga Arden et al. 1949, 1934 Chen, C. et al. 1954 Jay 1955); or compared the observed effect of different sophisticated iieren (Blume 1930 Eddy 1941 Bohemian 1948 W Itu ;. 1948 Strieder 1949).
Measurement of spontaneous motility
From the starting idea that the zentralnervo- sen disorders of an animal is the best in its ausdriieken unaffected movements, and m the desire to make the registration of such movements automatically, an attempt was made to measure the Spontanmoti- quality. ••• ‘: •
The simplest method is to use a BIIH round, white, sooty Papier.es of 25.5 cm diameter is placed under a bell jar. In this paper, a mouse is placed (Forst 1938), which more or less leaves white marks walking around. All is changed, the paper 30 min, and the evaluation is carried out by viewing the black and white.
, Distribution. Such papers are then also .in, displayed the publication. There were not only the quantitative differences in drug effects, but also various types of motion were read but a numerical analysis was by F orsts view midit ‘possible. ‘1: r •
In principle, similarly went Rothlin u. Cerium letti 11952) ago when s, ie a mouse fluorescent Ken on his back and then painted in the dark room. Camera for registration on the animal left open. To obtain the most uniform possible level of activity, they used mice with congenital rotation addiction. what a general application of the method difficult. Aspen cages Mechanical registration of spontaneous motility takes place in so-called “jitter cage”, which exists in numerous variations. • “
The oldest model of ist’wohl to a spiral spring lpâçer up hung box, Det «$ I at jeder1; Change in position of the seated therein mouse moves. Dio movements are transmitted by a cord that runs through ‘a © Holle, on a lever .größere or smallest on a r, slowly rotating kymograph. Aüs- ■ blows to the time abscissa with various’ .; Aufsifiréibt frequency, a variation is .Also the clack is with elektrisdien contacts of Forestry (1939); ferner.kann to the animal’s ear .By ‘a thread over a Bolle directly. connect a Sdrreiber and so record the movements (Perez-Cifeträ 1936
D ruck rey, u. K. .. ö h 1 he ‘1936 Dru ckr cy, M ü I le r Stuhlmann 193?,. W, E-art RNDa-nn 1951) 1
The following objections have been mainly against die’.Verwendung this Zitterkäfige’L’gemacht ,,:
1. changes in the environment such as changes of light and temperature or noise affect the animal, thus resulting in an irregular blank; this interference must either be switched completely aüs- or by repeated stimuli (Haas u. Z IPF 1949) as sounds and flashes of light are covered.
2. In the measurement event of two completely different factors, namely, the motor and the Sppntanöität that do not add up distinguishable in the measurement result.
3. The normal values are very inconstant; there is such. as circadian rhythms (ed Harn et al. 1952), Lebenscyc- len, individual differences.
4. The distance covered by the animal path in the box can be quite different at the same frequency rash.
5. The movement of the cage as a result of a ‘change of location of the animal affected by this; it is time “neurotic”.
The latter objection is a methodical improvement essentially overcome worden1, you by now in a style lying cage antenna mounts (Kniazuk u Molitor in 1944.) Or the animal can interrupt a zig-zag light beam by its running; Registration is done (u winter. Fiata- ker 1952 Dews 1953) through a photocell.
It may be said that almost all warm-blooded animals have been used for such a registration, the bird until the dog. The onde of H 1 finches used Ink (1952) (Fringillidae) do not have the special property that they sit quietly in light sleep on the pole, in deeper anesthesia-like sleep but on the ground, what you register differentiated two different Mareykapscln and Schreiber can.
A survey of the substances that have been studied with this method Me:
Caffeine was often .geprüft (S to r ni v at Le EU 1921
»S n MI m B H “e” i KB | p
f, e r 1 D et ai nckrey. v • 1955), where even the mini
times ‘* effective’ dose ‘the’ effectiveness
Spontaneous motility served as a favorable starting level for Prutung seda tive • drugs …;
Amphetamines and T-phenyl-2-methylaminopropanhyd ^ ^ (pervitin, – WZ) were affner of H (19 7)>. Zipf (1949)
Abreu et al, (1946), at W he ma n (1947). Dews (1953)
. MId ili KM | 1 0Ui nCye ■ VntStDundWeiníleut¿
motilFtätsstefgerrid J antagonistically
Sins, which, however, is to connect to the increased Ahma e ne te zwe period1 decreased activity, (A ^ eu et aI. 194b)
oSt h’u n ‘u.1 H l ^ K EinfsVtema-
tFdie by examining 75 sympathomimetic amines carried Ä-ib ^ Sc hu I t ‘bt al, (1941).
Strychnine can be better enträler prior ¿. Attenuation, i’m “jitter cage” check § | Sc h 1 1 1 agintwe 1928 Haas u.
% IPF 1949 “Iîté ‘V S 1953). ‘. <1 ‘J’ -‘3
Show cajbonsäurediiäthylamii.dj (Coraman, WZ) HMI Pi’kro’toxin, with this M ethod-e- • ig ^ mies-sensor – in ^ / Other centrally-causing substances such as Pentanr ^ hylentetrazol ÍCárdiazol, WZ) pyrid? , | a motility i tätS’SteigeTnde effect. only near the Dost, the convulsions heryor- calls (TEI AFFN; he lilj D1 i 1 1 e u n HazLeto 1939… Schulte al 1939 H aas u Z IPF, 1949 D ews 19 * 53). ,
Morphine and some similar compounds also showed significantly motilitätssteigerudd effect in Zitjfcerkäfig, particularly m high doses, and the effect of antagonistic and synergistic .Substanzen can s I / hite r quantitatively beautiful witnesses (Forst 1939 W i ri t he n. Flataker 1952 W it Termann 1951 tri PJJ 4;. et al 19 ^ 4, M 1 or a li y I955).
Hypnotics, sedatives and antipyretics showed not always clear motilitätsvermindernde effects (Schlagintweit 1928 Ho n d eli nk 1932 ;, Perez – Ci RERA 1936 Druckrey u.
h 1 e rv 193’6, Kochmann u. Kunz 1936 Druckrey et ILR 1937 Forest 1938 v D i 11 e u. Hazleton 1939 HAU rs chi 1 id. , 1939 From re ir ‘et al. 1946, Haasu. Zipf 1949 Harding ii ed; et \ al. 1952), they often act biphasic (Haasu Zipf 1949), d. ‘/ Fodie sedative’ Wirküng- occurs only after a short ER. , regunigsstadiiim, and they show strong individual besonderis Wjrkunigs.sAwài ^ unige’n-. . Again, the test, the effect often cheaper after any previous drug arousal, eg by being èoffein; or Mian out the test while! Dier increased activity -d;. ^ animal ‘by so ODEC only at night only during the day (Ho n Deli, nk 1932).
Individual work on ephedrine (H Arned et al. 1952), Phe nergan, Diphenhydraminhydro’dhilo’rid (Benadryl, WZ, Weidmann 1952) Thiamine (Kniazuk u. M o 1 itor 1944). Secale- , alkaloids (Rothlin u. Cerletti 1952) ,, cortisone (Winter u, F 1 a taker 1952);. Raujoolfia serpentina . (Serpasil, STC, Tri PXO d ‘et al 1954), alcohol (Hauschild 1939) and. Scopol- amine atropine / (A Breu et al. 1946) are only mentioned here.
The method is safe and easy to perform, the evaluation offers no special difficulties. th. “All substances are divided into three groups organize, namely those which inhibit the spontaneous motility, such that you. Request or indifferent. They can be extended by pretreatment with antagonists of various kinds to further differentiate the effect and make more accurate. A brief overview: ^ :, the results have been published 1929-1947, are Reed (1947). He is still firmly in summary: analeptics stimulate, activity, but home they men after repeated application. Some agents, such as cocaine, amphetamines and ephedrine show after repeated application habituation phenomena, running drums Another method, which the spontaneous motility mißt1, running drums used.
The animal, usually a mouse or rat, is set in a wheel that can rotate Sidi only in one direction. At an odometer, which adds the revolutions of the drum, one can measure the distance traveled by the animal spontaneous way exactly. The method is not ‘¡Sil worden- often used for testing drugs but they should be fairly accurate values, as, fluctuations in untreated animals are not large (Reed 1947). It checks the ‘Bffiíff ¥ lttel * a§s and sedative at night, since then the
Ettektam clearly stands out from the straight reverse activity level of the animal. So z. As phenobarbital showed during keinGVerände-
flncteF • EinnußUftatlBke, t ” on the other hand atte nadlts einfn deutliA damper
The following pharmacological works that use the revolving drum method, are “v ° n.Reed known f: Stewart (1898) examined the effect of alcohol not only on rats eve Z (S ™ M” me out of work be – and squirrels dogs
ik “? ™ rsufe ^ wi kung of Benzedri Jak Way (1938) administered to cod liver oil vitamin D fre.er, at; Koch (1939) gave various barbiturates and sedative acting Pflänzenextrakte; Carl
Son (1941) and as animal feed animals thyreodektomiorte them again thyroid; Marx (1950a) gave gossypol (WZ), an appetite depressant substance *); Brady (1953) gave tetraethylammonium.
Interesting are the different results that were obtained with two so similar methods as jitter cage and running drum (Heed 1947). Caffeine. Nh trazol and picrotoxin reduced z. B. the running ity tfk- it. while, significantly increased the spontaneous motility, registered with the cage Zittn. The interpretation of such a difference is not yet succeeded; its presence warns but caution in the transfer of results from one method to the other.
The run away to the rat from the start just crossed up to the feeding station, distinguishes itself from the revolving drum by the fact that the animal has to learn a task here. Apart from the term the S can tart – measured time; various obstacles and characters can go dupes. Miller u. Miles (1935) investigated in this way the effect of caffeine, Siegel et al. (1949) ethyl methylbarbitursaures soda (Nembutal, WZ) and Brady (1953) tetraethylammonium.
On a slowly rotating wooden or glass rod, the animal has the task to keep up. Using this method, compared Cross et al. (1955), the soporific Doriden known hypnotics, Tripod et al. (1954) Ráumolfia serpentina (Serpasil, WZ) with various antagonists. Skinner u. Young (1947) they found suitable for the quantitative determination of biological, curare.
Otherwise has become the testing of curare introduced a method and similar active substances more, when the hard stop ze “vol M a u, s (s au f ‘.éVi -‘ NEMS C’H räg’gestellt en D ra ht.gi animal is measured (Thompson 1946 Hopp Fe;. 1950 P e n u lika Unna 1952). This can be checked by one person ■ a large number of animals in a short time in the maze test.
The next and probably for testing! the abnormal behavior of animals most commonly used method uses the maze as a test apparatus. Here, an object is to the animal, almost always a rat, provided; by the proven quality differs mainly from the measurement of spontaneous motility. The evaluation methods are varied.
Before we a.uf the details of the method go, we want to make on a specific model, namely the so-called “elevated plus-maze-elevated maze” with the apparatus familiar. The elevated maze is probably the most widely used and most comfortable- ‘first-to-use form of the maze.
A bar, 90 cm long and 2.5 cm wide, is mounted horizontally on two small feet 75 cm above the ground. The bar is so ‘wide that a healthy rat run it comfortably and also can threaten to. Imagine a second rack with bar! transverse to the first, so that the side of one end of the other touches we get, if we look at it from above, a T. The Rat ‘which arrives on the long leg of the T, has the choice of whether it is at right angles wants to keep running to the right or left. On der.einen side will now. either immediately or get to run to another corner, a, the end – a dead end so ‘on the other side, however, the path by appending WEF’T Gansterer strip continues around several corners around until he finally ends at a feeding trough ,
A complete, elevated T-maze, as he would often used is, for. Example of such a frame 19, includes 15 T-VerzWuf- ‘gongen the way, 15 45 em long dead ends and parallel routes are about 45 cm apart , This .Irrgarten can be changed in the scheme by changing the frame easily, making the task of traversing is new, but not heavy.
What are the data that one. With such just can measure equipment? There-there is a fundamental difference ¡whether one measures learning a particular maze, the execution of learned tasks, relearning or forgotten the learned or relearning. This can eg be the following numbers detected.:
3 vcrsdiwündete time (rest and running into dead ends);
4 ] number of stops and errors; _
5. Total time from start to feed ends;
i Abrutsche®, slipping etc .; • IT,
7. fe do task: learning time, Umlernzeit on a 2nd maze, time of oblivion, the Wiedeyerlernens etc.
All these data can be related to each other yet, give a relatively fine picture of the efficiency of the functions of the animal and are differentiated by drugs affect
enced. Who , ü
Perhaps the most serious concern that has been expressed to the general usefulness of this method is that you use hunger as a driver. Man is not only the uniform, to be controlled starvation rat dependent, but it can, for. Instance an appetite-steaming drug of a psychomotor memory Pretending that is non-existent in reality interference. -,
This led to the introduction of water-maze “in which the rat floating, achieved the goal to phase; here to escape from the water ‘ser forms the drive to traverse the maze. In the case of elevated maze can make the animals more sensitive by half saturation to drug problems, or you can watch their reaction when. Would Maze On unsolvable (R o / sle nzweig et al. 1955).
Einftjweitere! Variation of the apparatus is the circle 1 rrga rien (W at son 1914).
Bé, f | hm, run the individual ways in circular arcs, where from the outer to the next inner arch leads a passage. Each floor gene gang has a- ‘closed and an open side, the target is in the middle .;’
The advantage dies’er arrangement is that it can be easily ¡ton above photographed or filmed, what the observer relieved. Nor can the plan by moving the rings easily change.
More A US baufen the maze consist in the affixation of trapdoors to prevent the return lines. Designating the way with colors, etc. Even lighting, same smells and sounds from all sides are obvious prerequisites for the success of attempts an overview of the method are M i I it (1950), without, however, the pharmacological, problem particularly to respond. Many descriptions and pictures can also be found at munti (1933 u. 1950).
More than 50 works I have become known in de- rie.n using the maze pharmacological effects have been tested. Most was determined whether the psychomotor memory had improved or deteriorated in its performance. The problem has much to questions of human. medical back.
Glutamic acid was dissolved in 5 work, partly using very: numerous experimental animals studied (Marx 1948 a, 1949 Porter U. G rif f in 19 $, oy Porter, Griffin and Stone. 1951 ZIM J9 Ross 1944). Only a work (Zimmerman u.
1 0 Sr • u) Tnm / to your conclusion that glutamic acid causes an increase Flqr Leist Ling: all others deny such a result u i sqlbst if want to generate deficiencies with reduced performance in the experimental animals were previously. ‘
/ Tr ?? e ^ rt’lura 11Ild antipyretics. In 7 Working miiliia ms u O Brien 1937 ¡Evans were barbiturates’ u. Hinged 1940 B 0 ughton 1942 M ARX 1950b, Armitage 1952 rose zw¡e 1 g et al. . 1955) and antipyretics (power and Bloom 1921 B oto ghton 1942) examined the effects oh the part interested the acute effect of one-off or re – HIB H the effect on the offspring of treated mother (Arm, Day 1952). Es’wurden- always depressive yWMPlWilBB it seems that learning more influenced UNRL Akßt a S-df iB? Eruibt ÌlaltlÌS Elner task (Williams u. O’Brien IH from two works (Boughton 1942 Marx 1950b)
! s hiedbeldieaWe “LT,” deUÜich to RDA) sex-linked difference; the females were more sensitive
1950aUH fd e rnf950 5 | l¡SÍBi¡ work (… Meier u Bunch HcrdV J’Äc, Becker u Donnell 1952 Hurri- the u Sanders 1953) examined the effects of oxygen
WüaatfÄ & fvrflp’r “pip” • * “” a. ™ sissse
193lba, nBe1’nMràKrld BS Î il Mathias 1935 Maurer maze test ‘Ifldurch the
.? larly audited functions ANDEROL eemVadltlSJ> “g of complacency, the animal i nfäl, YFE °; Tachen dic AiUvnbf” ‘ l’A -the Sch “In Vitami nB-Maiigel scheinen’die v ^ riníen? ‘”
to lie. 9 authors (M ‘ut CVU T s »Sunsùger
Poe et al. 1936 a, b, 1937, 1939 vr ,, “Maure r 1935 a,
ha rd F et al. 1937 S t e of, 19371 rJ ‘® 0 F et ?> • 1937 Bernhard
1937) found an impairment
the performance in the examination dur * Don
DERS if the animals in the youth lack ¡phttei opines influence
har dt et al. 1937). One author (M a rx 1949) finds cores Emtluli
100 t thiamine per os daily for 4 weeks, j
Matthias (1935) lead the decreased Le 1 & 1 u “fffetitloiie- generally decreased activity of the animals and to Appetitlosig
kCiEinUodekr several shocks, particularly Elektros ^
the performance of rats in a maze betraAtli *. This
was confirmed several times to be. At the same time could P orter
u. Stone (1947) statistisdi significantly show that ether anesthesia during the shock reduces its harmful influence. The shock test method as mentioned in the introduction ‘. •
Strychnine accelerated Nadi Lash ey (1917) in relatively high doses of maze learning task; These were doses where tremors already occur. This could HMM »! (1929) can not be confirmed. The question needs to be Nachuntersu
^ Caffeine showed different results. So Lash finds ley (191 ^) after lower doses prolonged learning time, after high Doseh decreased accuracy; Power (1932) finds a stimulating W r- effect that can be observed after B Oughton (1942) only in females. Miles (1929) can not confirm at least an increase in performance in his experiments. , ,,, •
. Amphetamine, sc 0.5 mg administered daily, showed by Min – I owski (1939) only a reduction of power at increased activity (. see also this the results of measurements of spontaneous tility). I , ■ HHHHHHRHI
Metrazol in spasm-producing dose (L Oken 1941) decreased as a result the performance in the maze, while lower doses (Heron u. Carlson 1941), even for an extended period (Bunch u. Mueller 1941), causing no measurable reduction in performance appear. .
Morphine acts in the maze test coincident verscniech- ternd on performance (Miles 1929 M à CHT 1920 M acn ■ J JJ * a. Mora 1921 E ddy u. Howes 1935 S imon u. Ed dy 1935). In particular, the time up to which the animal starts to run, joli be substantially lengthened (Eddy u. Howes, Simo nu Lad y). The effect is reversible well (again, a comparison with the results of Spontanmotilitäts measurement seems interesting).
Alcohol can be in effect in the maze test clearly (Miles 1929), especially in nods rewarded Running (Miller u. Miles 1936) ,,! T
Tobacco smoke called a Yerbesiserumg eter Erlernunig the maze to lower doses produced (P echst a u Reynolds in 1937.); Philips (1937) found no measurable effect. ,
Individual studies were conducted with thyroid (Carlson 1941), Allylthiourea (Scow 1946), adrenal cortex (Wenrick 1935 Ries S 1947), the determination of cholinesterase in the brain (K computing et al. 1954), Diisofluorophosphat (Platt u. W ickens 1950 ), chloroform, ether üüd. Nitrous oxide (Power 1920), opium alkaloids (power u. Mora 1921 E ddy u. Ahrens 1935), cocaine (Miles 1929)! VHyoscin (M i 1 is 1929), adenine (Power 1932), pregnenolone, a precursor of adrenocortical hormones the (M cGinnies 1947), insulin (Berman u. R IESS 1942) and amino acids (Zimmerman ü. Ros SF 1944). Enumerate the results here would take too long.
In summary we can say that the psychomotor pattern when it is once formed ‘, stable and reliable work; which blanks are so satisfying evenly. The test can be made more or less sensitive by saturation of animals and other measures. It can be analyzed in many different ways. His execution and evaluation requires a lot of effort and time. You can usually leave an animal only once run daily and it takes an average of about 20 runs (8 to 31), until it has learned the task. This and the mainly psychological problems seem to us the reasons for it to be, which is why so far there are few available test series, which are interesting for pharmacologists.
The use of conditioned reflexes The change of a conditioned reflex has been frequently observed to test the effect of drugs. Besides, many different types of reflexes were used. Since it is impossible to describe all the variations of this method even with some completeness, I want three different pick out, which seem to me to be for entire groups of tests typical. The enumeration of the attempts made with drugs “is then no finer differentiation of methodologies, which makes a comparison of results impossible. Unfortunately, my works of Russian writers were not accessible – to appropriate requests for literature I received no reply. This is unfortunate, because it seems that many pharmacological experiments have been made with conditioned reflexes, especially in Russia.
1. The simplest type of apparatus was z. B. from C. oisier our V et al. (1953) to test the chloro- promazine Largactil (WZ) used. A rat has to climb on a ringing signal is a vertical bar to prevent electrical shock at the cage floor. Through the effect of drugs they can now be either motorized unable trainees this
lead. “(S 111 e age 1936), or they Stôîun-
neglect tion, without itself engine s
Gen noticeable make (Courvoisie et al. l “m
2. The second when picked out recordable method ^
uses the so-called Skinner box S kin net u. Heron 1937). Herein, the animal by pressing down a button (which is registered by elekt clock) can be from time to time a cud chen roll out. Depending on whether you rewarded a certain number of keystrokes, “of whether one, regardless of the printing speed, the wage na, are certain time, form two different ‘
rhythms out the z. B. against Pentobarbita differ sensitive (Dews 1955a). The Regis belt tion is complicated, but fully automatic and ertor- changed not the presence of the experimenter.
3. In the third type, the animal is brought into a conflict situation that the conditioned reflex, after it is firmly settled, by shock (eg. o. blowing) is disturbed during recording of rewarding food. The animal is experiencing a conflict between the tendency to feed – as usual – to the signal to get back and the opposite tendency to flee gas on observed typical behavior is suppressed by certain central nervous system closely circumscribed angreilende substances without other physical side effects occur , This method could acobsen J u. Skaarup (1955) of a large number of chemical compounds which brauchbar- for them
: First to find out.
The following substances have been studied by means of conditioned reflexes of various kinds:
Barbiturates – were tested most frequently; dlabei S’ch’eiú’t consistent Reflexzéit ‘And the task (motorisai) Klher to be affected, as the reflex as such (Setti age in 1936 he tit u 1 in g u. i M II he 1941 Bailey. Miller 1951 D EWS t ^ ‘a,. b, Bättig u G randje a.ii 1955 Holten u .. Sun 1955). Barbiturates grab, apparently non-centrally specifically in the reflex pin. ‘•,
Alcohol was by S et 11 Age:. (1936), M ater in on (1945), Conger (1951), Jacobsen and Skaarup (1955b) and H o 1 – t e n u, l> omne (1955). examined. He seems to prevent reversible in conflict situations especially the development of a “neurosis” or their continued existence.
Scopolamine influenced by Dews Í 1935b), that behavior of pigeons in Skinner box does not appreciably while Jacobson n. Skaarup, (1955b) i u. U Holten. Sun (1955) a schwa / che Wirìfling with its method in conflict situations found.
Morphine influenced inversely by W ik 1 er et al. (1954) rats in § ki ji nerr chest, but after u .Holten. Sun (1955) Do not you see ‘,,. no u re d Ishi ‘behavior in conflict situations.
Tetraethylammonium slows the animal, leaving the startle response are lower, A u d 1 (1951) as, Fear vermin- pointed-promoting effect, Davitz (1953) as preventing the extinction ‘of the learned, Brady (1953) as a reduction of the motor activity. This clearly shows how difficult is an explanation even clear test results with animal psychology methods.
Individual studies: Prostigmin was from James and Ginsburg (1949).. Atropine and chloropromazine u of Holten. Sun (1955), Rauroolfia serpentina (reserpine, WZ) of Dews (1955) and Holten u. Sun (1955), benzilic-dimethvlamino- ethyl-HCl, Benactyzine, WZ) by Jacobsen u. Sun (1955), Vitaöiin B, deficiency of Zella Luria (1953) and Biel u. Wickens (1941), with and without shock ether by Hunt et al. (1953k: caffeine and amphetamines by Skinner and Heron (1937), B ä’ttig u Gra njean (1955), streptomycin and its derivatives -B e ¡1 ETTR “*, al ¡Hi curare and guilds… Culler (1937) and Harlow u. S et 11 age (MW), glutamic acid Z from are n_k o et al. (1951) and M agues rum deficiency of Patton u. L azo V LK (1946) tested.
, In summary it can be said that the comparability of results of different authors difficult by the variation of the methodology, the method extremely sensitive but appears as such on the effect of drugs and differentiating. A summary also indicates the contradictory results, can be found at Munn (1950).
The three tables Test
J &; Fael ^ tunity to combine two separate impressions
Ä: Jlfl ™ nm Ti em Three tables test?!. The rat learns at different times, to know food and a certain form table, then the attempt by combining
w ii hl e n 0 n T he $ fa fj! lln ^ he ^ tables the right to
turns finest oil primarily to ver
sen (z. B. M ay ESJ lllifll nadl to measure Dirnresektion
Phenobarbital (11 n ^ Midfgcveímn) ” ‘y nn’Ti’ Abp1 * a (> 011 by name
d EU tildi c BeeinträditigungCier power ^ <“”> g
holding “damage / if ^ ie ^ ^ animals Bleâîi vnterliefl only other long were. fed deficient in morphine addicted monkeys
perform better than before after NT1 AB 8 (1940) 1
had, rats were 1 Is® to H ami. ® * 9 ■ infection get glutamic acid shares the task srhnpllo u \. Mow r (1947) to Hong Hurst (1950) found for R “11”! Lnd Maier u.
Rates wachsendcn better performance than without ^ acl’ose * 086’01’1 * b “
INACH another method must ri; t 0: i 1
between ZW-egg options (eg. as two versdüeden bright luren) verscmeden to distinguish,
“FRjHM of * 3 MMEB 19 ^ M way
u. L eo nardllMll “BIMS result, Burnham reoidektomie, Marx * llBBl w “ ^ “^ Pj sektomie and thymus of pentobarbital, Fr omherz ^” Application
defTkbtkrauAel! ‘1 “and morphine and Philips’ (1937) ° ° RDE n’Einfluß
The superficial comparison of these and the previously
MHMsdieint the MI H
less sensitive for disorders through medication
MP + vr ^ iron JlUr • elne.jn? ™ 11 d 1 ee assessing the iVietlioden have not been applied consistently enough.
Amendment innate behaviors R Em probably standing until the beginning of his possibilities of development process for testing of drugs represents the observation and registration of congenital, more or less stereotyped behaviors expiring.
Most frequently, the influence of .Sexualhormonen was on, described the sexual instinct. This Hamilton the Copulationsverhalten is divided by the uniformity of the observation’s sake in 4 to 7 stages, the occurrence or absence can then be quantitatively evaluated by a point system (Ball 1937, 1939, 1940, Stone 1938 Sollenbeigef u. 1939 Seward. 1940 Beach u. Wood tuck it in 1949, Birch u. Clark 1950 Grunt u. Y o un g 1953). It is regularly found an increase in measured as “sexual instinct”.
Bruner u. Cunningh on (1939) find the Copulai ion faced down ten to thymus extracts reduced Stellar (1951) found no effect of thyroid sen preparations the hamsters while Evans. . u K 1 app (1940) by feeding thyroid extracts to Anolis carolinensis faster and more violent reaction in defense of their, territory observed; Chance (1948) describes a strange effect on the social behavior of mice under the influence of amphetamine, Joel u H inger (1926) the presence or absence of abstinence symptoms in rats after morphine and other central Analgeticis, Stone u. Walker (1949) a strangely disturbed nesting behaviors of pregnant rats to shocks; the same shocks, m ether anesthesia applied, leave the nest building behavior unaffected. Witt (1956) summarizes a series of works in which the disturbed through medication behavior of spiders build their networks in the photograph is measuring detected.
Summary and conclusion: HHH
We can conclude that animal psychology methods are ideally suited for detecting the effects of drugs that affect the central nervous system. They have more to ver resembling investigation of various substances i Losse ^ Sen bfwährt as to clarify problems
i «« bail-■
Collection gg | g ■
“IMHHI” nd IHRC He ‘
results will be described.
WfíMí Animal Psuchology used in Drug Research
IH A HBB
the identification o They have Proved Father
of different substances rather than for the elucidation of the problem of human psychology. In order to obtain useful information in Drug Research, it is more important to compile experience in large test series than to develop new variations of methods. Methods of animal psychology are well worthwhile in Experimental Pharmacology provided They Can not Be Replaced by other methods. The most important methods of animal psychology and the results yielded They are described.
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