STUDIES ON BEHAVIOR. II. THE EFFECTS OF PEXTOBARBITAL,

METHAMPHETAMINE AND SCOPOLAMINE ON PERFORMANCES

IN PIGEONS INVOLVING DISCRIMINATIONS’2

PETER B. DEWS

Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Received for publication June 27, 1955

The application of the Skinner box technique to study the behavioral effects

of drugs has been described in a previous communication (Dews, 1955). The

work was done on pigeons; the birds were intermittently rewarded with food

for pecking a transilluminated plastic disc (the key). Two different schedules of

reward were used; each gave rise to a characteristic pecking performance. The

two different performances showed differential sensitivity to modification by

pentobarbital. The schedule of reward was thus shown to be a relevant environ-

mental variable in determining the behavioral effect of pentobarbital.

It is a characteristic feature of this type of behavior (“operant behavior”-

Skinner, 1938) that it may be brought under “stimulus control”. If a pigeon is

rewarded according to an appropriate schedule for pecking the key when certain

suitable environmental stimuli3 are present, but is never rewarded when other

stimuli are present, then the pecking performance comes to differ according to

which of the stimuli are present. The pigeon “discriminates” between the stimuli,

and behaves more or less appropriately to each. Alternatively, it may be said

that the stimuli “control” the behavior of the animal. In the present work, the

effect of three drugs (pentobarbital, methamphetamine, and scopolamine) on

some aspects of such discriminatory behavior has been studied. It has been

shown that these drugs, in doses up to those abolishing all pecking behavior

under the conditions of study, did not interfere with the differential performance

to a simple pair of stimuli. On the other hand, when a more complicated set of

stimuli was used, it was found that pentobarbital, and methamphetamine but

not scopolamine reduced the usual difference between the performance when the

stimuli were appropriate for rewards and the performance when the stimuli were

inappropriate for rewards.

MATERIALS AND METHODS. Apparatus. The Skinner pigeon box previously described

(Dews, 1955) was modified for the present work. Four different colored bulbs (G.E. C 71/2) were arranged so that the key could be transilluminated by any one of them, giving

four possible “key colors”. In addition, a 12 watt source of white light was put in the roofof the pigeon compartment at the opposite end to the key; this light (the “house light”),when on, brightly illuminated the whole pigeon compartment. Hence 8 different combina-

1 This work was supported in part by funds received from the William F. Milton Fundof Harvard University, and in part by funds received from The Roche Anniversary Foun-

dation of Hoffmann-La Roche Inc.

2 A preliminary report appears in Fed. Proc., 14: 322, 1955.‘The term “stimulus” is used here in its usual physiological sense of an environmental

influence which causes, or tends to cause, a change in a living system.

380

The symbols S+ and S- as here defined correspond to the symbols SD and S� respec-

tively used in the psychological literature in this field. S+ and S- have been used for

typographical convenience and because they suggest their meaning more obviously.

STUDIES ON BEHAVIOR 381

DIAGRAMMATIC REPRESENTATIONOF SCHEDULES

DRUG

CONTROL AFTER DRUG

SCHEDULE SERIES 5,j, SERIES

1

2

3

4

R+ � R+� � R+� R+� R+

B �R+� W+W%� B�R+�W+�

0 30 45 75

TIME IN MINS

NO LIGHTS REWARDS

+ HOUSE LIGHTS ON �J NO REWARDS

FIG. 1. Diagram showing sequence of stimuli in the various schedules used. R, B, Y and

W indicate that the red, blue, yellow and white lights respectively were on behind the key.

tions of stimuli were possible, viz. 4 different key colors each with or without the house

light; of these, 6 combinations were actually used. In the presence of certain of these com-

binations, the pigeon was intermittently rewarded with access to food for 4-5 seconds for

pecking the key; these combinations of stimuli will he referred to as S+. In the presence

of other combinations, the pigeon was never rewarded; these combinations of stimuli will

be referred to as S-i. Responses made in the presence of S+ and S- were counted sepa-

rately on digital counters; in addition a permanent time-cumulative response record was

taken in all experiments, as previously described.

Schedules. In the presence of S+ rewards were arranged as follows. For a predetermined

period of time following a reward (or the start of the S+ period) no peck was rewarded;

when this time had elapsed, the first peck made was rewarded. The minimum interval

which necessarily intervened between successive rewards was not constant; in the present

work 15 different intervals were used, varying from 0 (two consecutive pecks rewarded)

to 2 minutes, with an arithmetic mean of 1 minute. The sequence of the intervals was

randomly determined in the first instance but then kept the same through all the experi-

ments. This scheme is an example of a “variable interval” schedule of reward in the ter-

minology of Skinner (1953). In the presence of S-, by definition, the pigeon never received

any food.

In definitive experiments, S+ and S- were presented alternately, each for 5 minutes.

The changeover from one to the other was abrupt. Three alternations, giving a total pres-

entation of S+ and S- of 15 minutes each, comprised a “series”. Each experiment started

382 PETER B. DEWS

with the bird waiting 15 minutes in the completely darkened box, followed by a control

series. The pigeon was then removed from the box, injected with the appropriate dose of

drug (or saline alone) and immediately replaced in the darkened box. The after drug seriesstarted 15 minutes later.

Four schedules, which differed according to the combinations of key color and presence

or absence of house light constituting S+ and 5-, were programmed. The arrangements

are shown diagramatically in figure 1. It will be seen that in schedules 1, 2, and 3, S+ and

5- differed in a single constant feature, viz., either key color (schedule 1) or presence orabsence of the house light (schedules 2 and 3). On the other hand, in schedule 4, not only

were there 3 different 5+ and 3 different 5- but, in the first four periods of a series, thecontingency associated with each individual stimulus was conditional; neither the key

color alone nor the presence or absence of the house light alone characterized the stimuli

as S+ or 5-; e.g. the presence of the house light was part of an S+ combination when thekey was blue; but was part of an 5- combination when the key was red. In contrast, inthe last two periods of a schedule 4 series the yellow and white key colors uniquely charac-

terized the stimuli as S+ and 5- respectively exactly as did the red and blue key colorsof schedule 1.

Procedure. Male white pigeons of between 400 and 500 grams weight were maintained

in a standardized state of food deprivation (but with constant free access to water) and

were trained to work in the Skinner box, as previously described (Dews, 1955). They werethen assigned to the various schedules just described and run once daily, most days, until

the completion of the experiments. The programming circuits were arranged so that eachpeck in the presence of 5- could be made to reset the timer which was timing the 5 minute

period of presentation of S-. Thus, when this “5- renewing” device was in operation,the 5- periods continued until the pigeon had not pecked for 5 minutes. In general, 5-renewing was used only during training of the birds; it was never in operation during de-finitive experiments. Stable performance developed much more slowly on schedule 4 (2-3

weeks) than on schedules 1, 2, 3 (4-5 days). Three pigeons were studied on schedule 1, one

each on schedules 2 and 3 and two on schedule 4.Pentobarbital sodium,’ methamphetamine hydrochloride’ and scopolamine hydro-

bromide7 were dissolved in 0.9 per cent sodium chloride solution and were injected intra-muscularly. Doses are stated in terms of these salts and give the total dose given to thebirds. The various doses of each drug were given in random order; each dose was given on

two occasions to the same pigeon. In general, where more than one drug was studied in thesame pigeon, the observations on one drug were completed before starting observations onanother drug.

Measurements of drug effects. Two indices have been used. 1) The output ratio (O.R.)

was defined as the ratio of the average rate of response in the presence of S+ in the after

drug series to the average rate of response in the presence of S+ in the control series inthe same experiment. It is thus a measure of the effect of drugs on performance in thepresence of 8+. 2) The discriminative ratio (D.R.) was defined as the complement of theratio of the average rate of response in the presence of 5- to the average rate of response

in the presence of 5+ in the same series. Hence if the pigeon does not respond in the pres-ence of 5- but responds in the presence of 5+ in the same series, the D.R. is 1; while if

the rates of response are identical in the presence of both 5+ and 5- the D.R. is zero.

RESULTS. The 1 minute variable interval schedule of reward, in operation

during all the S+ periods, gave rise to a relatively constant rate of responsethroughout the time of presentation of S+ (see figures 2 and 3). While the

average rate varied amongst the pigeons from less than 60/mm. to more than

‘Generously donated by Abbott Laboratories.‘Generously donated by Burroughs, Wellcome & Co.

Generously donated by Merck & Co.

RESPCNS�

RtSPONS(S

1000

500

3 MGPB

STUDIES ON BEHAVIOR 383

FIG. 2. Effect of pentobarbital on performance on schedule 1. Ordinate and abscissa

scaled have been superimposed on an original record. The short diagonal lines on the origi-nal record show the occurrence of rewards. Below the record is a key showing the

nature of the stimuli throughout the run. The conventions in the key are the same as thoseof figure 1. Note almost complete absence of responding in 5- periods and the lack ofeffect of 3 mgm. pentobarbital on performance on this schedule.

0

FIG. 3. Effect of pentobarbital on performance on schedule 4. Note almost complete

absence of responding in S- periods before drug, but large number of responses in thesecond S- period after drug. Performance in S+ periods not obviously affected by thisdose of pentobarbital.

384 PETER B. DEWS

* When saline alone had been given.

TABLE 1

Pecking performances of pigeons during control series

Pigeon No. Schedule No ofExperiments

Mean No. ofPecks in 15 Mins

ofS+

Mean No. ofPecks in 15 Mins

ofS-Mean DR.

1

2

3

45

67

1

1

12

3

4

4

40

40

2411

15

3340

858

1257

1955

920

905

981906

2.1

4.6

8.70.33.0

23.319.9

>99

>.99

>99>99

>99.98.98

130/mm. (table 1), it remained relatively constant for any one pigeon (average

coefficient of variation 15 per cent).

On the other hand, the rate of response in the presence of S - fell to very low

levels (figures 2 and 3, table 1); i.e. the D.R. became close to 1.

Injections of drug or saline were given only when the D.R. of the control

series exceeded 0.9. On 6 occasions with schedule 1 and on 9 occasions withschedule 4, the D.R. of the control series was less than 0.9; these experiments

were not continued, and the figures from them are not included in table 1.

Performance on schedule 1. The control performances of birds on schedule 1

are summarized in table 1. In all except 3 (out of 104) experiments, the D.R.

was greater than 0.99 (i.e. the average rate in the presence of S+ was more than

100 times greater than in the presence of S -). In 20 control series there were

no pecks in the total 15 minute presentation of S -‘ and in a further 41 there

was only a simple peck; more than 5 pecks were made in only 16 experiments.

Following saline, the average D.R. was again 0.99 or higher (table 2). Bird 1

rather consistently showed a slightly higher average response rate in the presence

of S+ after the injection of saline than before (O.R. > 1); the opposite was

true for bird 2 (O.R. < 1) (table 2).

Effect of drugs on performance on schedule 1 (table 3). The effects of pento-

TABLE 2

Summary of saline control experiments

Pigeon No. Schedule No. No. ofExperiments Mean O.R. Standard

Deviation

Mean D.R. of

“After Drug”Series’

1 1 10 1.05 .059 > .99

2 1 14 0.82 .098 >99

3 1 13 1.01 .108 >99

4 2 2 0.93 - >99

5 3 2 1.02 - >99

6 4 8 0.88 .092 .98

7 4 9 1.04 .096 .95

‘SE. = .063. ‘SE = .025.

STUDIES ON BEHAVIOR 385

TABLE 3

Effect of pentobarbital, methamphetamine and scopolamine on performance on schedule I

Pento-barbitalDosage(mgm.)

Mean’OR.

Mean’D.R.

Metham-phetamine

Dosage(mgm.)

Mean’OR.

Mean’DR.

Sco�olamineosage

(m�.)

Mean’OR.

Mean’DR.

04 0.90’ >99 0� 0.926 >.99 0� 1.05� >991.0 0.91 >.99 0.1 0.98 >.99 0.001 1.02 >.993.0 1.00 >99 0.3 0.78 >99 0.003 0.87 >.99

4.0 0.22 >99 1.0 0.27 >99 0.01 0.76 >995.2 0.01 >99 1.7

3.0

0.22

0.01>.99>99

0.0170.03

0.64

0.14>99>99

0.0520.1

0.080.02

>99>99

‘Mean of birds 2 and 3. ‘Mean of birds 1 and 2. ‘Bird 1 only. 4Saline alone.

‘SE. = .074. ‘SE. = .067. 7S.E. = .059.

barbital were studied in birds 2 and 3 (figure 2). Following doses of 4.0 mgm.

or 5.2 mgm., the average rate of response in the presence of S+ was greatly

reduced; but at no dose level did the average D.R. fall below 0.99.

Similar results were obtained with methamphetamine on birds 1 and 2. At

no dose level did the birds show any increase in the number of responses in the

presence of S -, although doses of 0.3 mgm. or more caused pronounced be-

havioral effects, as shown by the fall in the average rate of response in the

presence of S+.

Scopolamine was studied in bird 1 only. Again, even doses sufficient to affect

performance grossly in the presence of S + caused no breakdown of discrimina-

tive behavior; the D.R. never fell even to 0.99.

Performance on schedule 4. The average D.R. in the control series of birds 6

and 7 working on schedule 4 was 0.98 (table 1, figure 3) indicating an approxi-

mately 50 fold difference in rates of response in the presence of S+ and S -.

Both the O.R. and D.R. were well maintained in experiments in which saline

alone was injected (table 2).

TABLE 4

Effect of pentobarbital, methamphetamine and scopolamine on performance on schedule 4 ofbirds 6 and 7

Pentobarbital Methamphetamine Scopolamine

Dose MeanOR.

MeanD.R.

Dose MeanOR.

MeanD.R.

D�eI

Mean MeanOR. . DR.

0

1

3

5.2

0.95’

0.97

0.97

0.36

0.95’0.93

0.82

0.06

0

0.1

0.3

0.52

1.0

0.951.00

1.07

1.10

0.71

0.950.960.56

0.89

0.76

00.0030.01

0.03

0.1

0.95 0.950.86 0.97

0.50 0.98

0.30 >0.99

0.02 >0.99

386 PETER B. DEWS

* S.E. = .037.

Effect of drugs on performance on schedule 4 (table 4). The effects of all three

drugs were studied in both pigeon 6 and pigeon 7.

Following 3 mgm. of pentobarbital consistently more responses were made

in the presence of S - than following saline alone, although the average rate of

response in the presence of S+ was not much affected. This is illustrated in

figure 3. It will be noted that in this particular experiment, most of the responses

in S - occurred in the first part of the second S - period after the drug. The re-

sponding in S - often took the form of a period of steady responding, as here.

In general, such periods of responding were rare and short in the third S -

period (see below), but there was no obvious tendency for them to occur in

any particular part of the first or second S - periods. In spite of this variability

in the time of occurrence of the pecks during S -, the total number made through-

out the presentation of the various S - was reasonably constant. Following

5.2 mgm. of pentobarbital the average rate of response in the presence of S -

was almost as high as that in the presence of S+.

Methamphetamine in appropriate doses also caused a fall in D.R. to values

below those seen following saline, even when the rate of response in the presence

of S+ was well sustained or even increased. The extent of fall of D.R. was

variable, and over a considerable range bore no obvious relation to dosage.

However, since the D.R. following saline showed great consistency (coefficient

of variation 2.5 per cent) there can be no reasonable doubt that the lowering of

the D.R. by methamphetamine was a real phenomenon.

Injection of scopolamine led to no fall in the D.R.; on the contrary, discrim-

inative performance even improved following doses causing a fall in response

rate in the presence of S+.

As explained earlier (see Schedules) a schedule 4 series may be divided into

2 parts: an initial 4 periods in which the implication of the stimuli was condi-

tional; and a final 2 periods in which the implication of the key color was un-

ambiguous, as in schedule 1. The D.R. of each of these parts has been calcu-

lated separately for the after drug series following saline, pentobarbital and

methamphetamine. Following saline alone, the D.R. for the conditional part

was slightly, though consistently, lower than for the simple part (table 5).

Following the various doses of pentobarbital and methamphetamine studied

TABLE 5

Differential effect of pentobarbital and methamphetamine on performance o�f birds 6 and 7 in

“conditional” and “simple” discrimination situations of schedule 4

Pentobarbital Methamphetamine

Dose DR DR(mgm.) -� (conditional) -� (simple)

Dose(mgm.)

DR DR(conditional) (simple) -

0 095* >.99 0 095* >.991 0.79 >99 0.3 0.55 0.76

3 0.20 >.99 0.52 0.88 0.98

5.2 <0 0.85 1.0 0.57� 0.85

STUI)IES ON BEhAVIOR 387

TABLE 6

Effect of pentobarbital and methasnphetamine on performance on schedules 2 and S of

birds S and 4

Pentobarbital Methamphetamine

Dose OR DR � Dose OR -� DR

0 1.04 >0.99 0 1.04 >0.99

3 0.96 >0.99 0.3 0.81 >0.99

5.2 0.29 0.99 0.52 0.56 >0.99

the D.R. for the conditional part was always less than that for the simple part;

the difference was usually large as can be seen from the averages shown in table

5. It should be noted that the D.R. for the simple part did, on some occasions,

fall to values lower than any seen with schedule 1.

Performance on schedule 2 and 3 and effect of drugs. Performance on schedules

2 and 3 did not differ in any significant way from performance on schedule 1

(tables 1 and 2). Doses of pentobarbital and methamphetamine which caused a

fall in the D.R. of birds working on schedule 4 had no effect on the D.R. of birds

working on schedules 2 and 3 (table 6).

DISCUSSION. It has been shown that the discriminative performance of the

pigeons based on either a difference in key color or the presence or absence of

the house light was not disrupted by pentobarbital, methamphetamine or

scopolamine in doses up to those causing complete cessation of pecking. On the

other hand, pentobarbital and methamphetamine, but not scopolamine, inter-

fered with the discriminative performance on schedule 4, a schedule which in-

volved six different stimulus combinations and a conditional situation. These

findings are clearly in agreement with the widely held view that “more complex”

performance is more susceptible to drug effects than “simple” performance.

However, the terms “complex” and “simple” are not easy to define in this

context, and it would appear preferable to describe the differential sensitivity

to drugs in terms of the operational difference between the schedules.

The analysis summarized iii table 5 makes it appear that it is the conditional

feature of schedule 4 rather than simply the increased number of stimulus com-

binations involved, which determines this difference. However, the D.R. of the

simple part of schedule 4 did fall on occasions, indicating that it was not al-

together comparable to the completely simple schedules 1, 2, and 3. Moreover,

the constant sequence of stimuli means that the effect of the conditional and

simple parts of schedule 4 is confounded with time after drug. Further experi-

mental analysis is required.

Since the S+ and S- periods alternated, a change in stimuli always implied

a change in contingencies. Hence the changes of stimuli, rather than the nature

of the stimuli themselves may have played a part in the sudden changes in

pecking rate shown in figures 2 and 3. It should be emphasized that schedule

4 did not differ from the other schedules in this regard.

No attempt was made to identify the specific feature or features of the stimuli

388 PETER B. DEWS

on which the discriminations were based. The differences between the stimuli

were made as gross as convenient ; but it was not relevant to the present work

to determine whether, for example, the discrimination of schedule 1 was based

Oil the qualities of redness and blueness of the stimuli. There was, in fact, a

distinct difference in brightness between the red and blue lights, and no attempt

was made to balance them in this regard.

The absence of effect of scopolamine on the discriminations of schedule 4 has

no obvious explanation. The pigeons ate freely when offered grain following doses

of scopolamine abolishing pecking behavior in the Skinner box. Even a dose as

large as 10 mgm. scopolamine (i.e. 100 times larger than the dose almost abolish-

ing pecking behavior) caused no grossly observable change in behavior; 15 mgm.

caused vomiting; 45 mgm. still caused only vomiting with no other unequivocal

signs. From the point of view of the present work, the effects of scopolamine are

of interest in showing that the effects of pentobarbital and methamphetamine

on the I).R. were not entirely nonspecific.

At the appropriate dose level, both methamphetamine and pentobarbital

caused a slight increase in the O.R. The very modest “stimulating” effect of

methamphetamine seen in the present experiments is believed to be due to the

nature of the schedule of reward. The rate of pecking is of the order of 1/sec.

while rewards are set up only 1/mm. on the average. A doubling in rate would

mean that the rewards would be received at most only 0.5 sees. earlier, while

120 pecks/reward instead of 60 pecks/reward would be made. This decrease in

“efficiency” with increase in rate probably tends to minimize any increase in

rate above its already “inefficiently” high value.

The “S - renewing” procedure was used during training to prevent the

change from S - to S + (a rewarding event) from occurring shortly after a peck

made in the presence of S - ; such chance coincidences tend to maintain pecking

in the presence of S -‘ increasing the probability of further coincidences of peck

and change to S+ and thus starting a vicious circle.

SUMMARY

Pigeons were rewarded with occasional access to food for 4-S seconds for peck-

ing a translucent plastic disc when certain environmental stimuli were present,

but were never rewarded when other environmental stimuli were present. They

(Same to peck at a steady rate of the order of 60/mill. when the stimuli appro-

priate to rewards were present but at a rate of only about 1/mill. or less when

the stimuli appropriate to no rewards were present.

When the stimulus appropriate to rewards was a red light behind the traiis-

lucent disc and the stimulus appropriate to no rewards was a blue light, then

this differential performance was not disrupted by pentobarbital, methamphet-

amine or scopolamine, although as the dosage of any of the drugs was increased,

pecking in the presence of the red light was progressively reduced.

When the stimuli appropriate to rewards were a red light, a blue light plus a

differently located white light (the house light) or a yellow light plus the house

light, and the stimuli appropriate to no rewards were a blue light alone, or a red

STUDIES ON BEHAVIOR 38�)

or white light plus the house light, then the differential performance between the

sets of stimuli was reduced by pentobarbital and methamphetamine, but not

by scopolamine.

Preliminary analysis of the differences between the schedules determining

this differential sensitivity to drugs is presented.

ACKNOWLEDGMENT. The author wishes to thank Mr. Briah Connor for con-

scientious assistance throughout these experiments.

REFERENCES

DEws, P. B.: Tiiis JOURNAL, 113: 393, 1955.SKINNER, B. F.: The Behavior of Organisms, New York, App1eton-Ccntur�, p. 19, 1938.

SKINNER, B. F.: Science and human behavior. New York, Macmillan, P. 102, 1953.

MERCURIALS AND RENAL SH CONCENTRATIONS 399

TABLE 6

Effect of mersalyl on sulfhydryl concentrations in the cytoplasm of rat kidney cells (in vii ro)*

Incubation Time in0.02 .41 Mersalyl

Proximal Tubules(Terminal Portions)

Proximal Tubules(Convoluted Portions)

Distal ConvolutedTubules

EPer cent

ofcontrol

EPer cent

ofcontrol

EPer cent

ofcontrol

Saline (60 minutes)..1 minute

2 minutes

30 minutes60 minutes

.419 ± .012263 ± .009

246 ± .008

228 ± .008

203 ± .006

100

63

59

5548

.606 ± .009

.478 ± .009

.433 ± .008

.351 ± .007

.364 ± .010

100

79

71

58

60

.538 ± .008

.375 ± .011

.339 ± .011

.290 ± .005

.271 ± .007

100

70

6354

50

5 Each value represents the mean of 15 measurements in 15 different cells.

mechanism. It is possible that the pattern of sulfhydryl depression after mersalyl

administration may reflect the presence of two distinct reabsorptive mechanisms.

Although the collecting ducts generally have been considered to be passive

tubes which convey the formed urine to the renal pelvis, certain indications

that they play a role in reabsorption have appeared in the literature from time

to time. Schmidt-Nielson and Schmidt-Nielson (1952) cited the relatively

important role of collecting ducts of the kangaroo rat, Dipodomys, in water

reabsorption. Darmady (1954) correlated a resistance to Pitressin in patient.s

with diabetes insipidus and cases of death preceded by massive water diuresis

with marked atrophy of collecting duct epithelium. Wirz et al. (1951), on the

basis of freezing point depression studies, concluded that an osmotic drain of

water from collecting ducts to the hypertonic surroundings occurs in the rat

and hamster. Our data show an effect of mercurials on cells of the collecting

ducts and it may well be that mercurial diuresis is augmented by some inter-

ference in reabsorptive capacities of collecting ducts.

Fawaz and Fawaz (1954) found that the optimal diuretic dose in rats was

approximately 10-15 mgm. mersalyl/kgm. when given intravenously, and that

the height of water diuresis was reached in 2-4 hours. These results of Fawaz

and Fawaz have been confirmed in our laboratories. In a large series of experi-

ments, it was found that the maximum diuretic period following the intra-

muscular administration of 5-15 mgm. mersalyl/kgm. occurred at 2-5 hours.

Thus the pharmacological and biochemical events relating to mercurial diuresis

seem to occur simultaneously.

The effects of cysteine and BAL reported here are consistent with the pharma-

cological data obtained when they are used in conjunction with mercurials.

Earlier work by Handley (1949) and Handley and Lavik (1950) indicated

that mercurials inhibit the enzyme, succinic dehydrogenase. They reported

inhibition in kidney homogenates of rats treated with mercurials but Fawaz

and Fawaz (1951) were not able to confirm these reports.

While this work was in progress several reports appeared in the literature

suggesting that mercurials produce diuresis by inactivating succinic dehy-

drogenase. Mustakallio and Telkk#{228} (1953) injected rats with a mercurial diuretic