The effect of chronic administration of (-)delta9-trans-tetrahydrocannabinol on maintained

discrimination performance in pigeons

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Authors Sczerzenie, Victoria Johanna, 1950-

Publisher The University of Arizona.

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THE EFFECT OF CHRONIC ADMINISTRATION OF (-)DELTA9- TRANS-TETRAHYDROCANNABINOL ON MAINTAINED DISCRIMINATION PERFORMANCE IN PIGEONS

byVictoria Johanna Sczerzenie

A Thesis Submitted to the Faculty of theDEPARTMENT OF PSYCHOLOGY

In Partial Fulfillment of the Requirements For the Degree ofMASTER OF ARTS

In the Graduate CollegeTHE UNIVERSITY OF ARIZONA

1 9 7 4

STATEMENT BY AUTHOR

This thesis has been submitted in partial fulfill­ment of requirements for an advanced degree at The University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library.

Brief quotations from this thesis are allowable without special permission, provided that accurate acknowl­edgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his judgment the proposed use of the material is in the inter­ests of scholarship. In all other instances, however, permission must be obtained from the author.

SIGNED:

APPROVAL BY THESIS DIRECTOR This thesis has been approved on the date shown below:

Jo /Otsk,DateJOSEP

tant ProfejYONS

;or of Psychology

ACKNOWLEDGMENTS

I wish to thank Dr. Joseph E. Lyons for the conception and design of this experiment and for his unfailing support while it was being carried out. My thanks also go to Suzanne Shaw and Steve Minney for their conscientious assistance and to Dr. William D . Klipec for his exquisite competence as the man behind the electro­mechanical program, I wish also to express my appreciation to Drs. Clinton L. Trafton and Dennis L. Clark for their friendship and guidance and to Dr. Robert Lansing for his help as a committee member, And finally I wish to thank Faren Akins whose spirit and diligence in the pursuit of science has made him an invaluable comrade in the laboratory,

TABLE OF CONTENTS

PageLIST OF ILLUSTRATIONS ........ . . . . . . . . . . . vLIST OF TABLES . . . . . . . . . . . . . . . viABSTRACT ............. . . . . . . . . . . viiINTRODUCTION . . . . . . . . . . 1METHODS . . . . . . . . . . . . . . . . . . . . . . . 9

Subjects . . . . . . . . . . . . . . . . 9Apparatus . . . . . . . . . . . . . . . 9Procedure .............. 10

RESULTS .......... 14DISCUSSION o o . e o o . e . . . . . 21-REFERENCES . . . . . . . . . . . . . . . . . . . . . . 24

LIST OF ILLUSTRATIONS

Figure Page1. Relative response rates to distal,

proximal and S- stimuli as a function of sessions during discriminationtraining for Group E : Z-l, Z-5 and A-3 . . . . 15

2. Relative response rates to distal,proximal and S- stimuli as a function of sessions during discriminationtraining for Group E: Z-26,■Z-7 and C~5 . . . 16

3. Relative response rates to distal,proximal and S- stimuli as a function of sessions during discriminationtraining for Group D: Z-2, Z-4 and A-8 . . . . 17

4. Relative response rates to distal,proximal and S- stimuli as a function of sessions during discriminationtraining for Group D: Z-8, Z-6 and A-15 . . . 18

v

LIST OF TABLES

Table1.

PageOutline of drug and training

procedures „ „ , 12

ABSTRACT

Four groups of pigeons were trained on a fivestimulus, wavelength discrimination in which responding inthe presence of 53 8, 548, 566, and 57 6 nm was reinforced ona VI 1 schedule while responding in the presence of 555 nmwas correlated with extinction. The difficulty.of thediscrimination was varied by presenting the 555 nm stimulusduring either 20 or eight of the 40 stimulus presentationsof a session. Half of the S ’s trained under each of thetwo levels of difficulty were injected with ,25 mg/-kg-A^-

9tranS'-tetrahydrocannabinol (A TEC) for 20 consecutive discrimination sessions, while the remaining two groups were given the drug vehicle throughout discrimination training.

9In the subjects injected with A THC the effect of the drug on acquisition of the discrimination, on the development and maintenance of positive behavioral contrast and on generalization of inhibition was assessed through a counter­balanced design of 20 drug and 2 0 drug vehicle administra^ tions within the 40 sessions of discrimination training.The variability of performance evident within the control groups obviated any conclusions concerning the drug's effect on learning and inhibition in the pigeon. No evidence of disruption of performances peculiar to each bird, however, was seen upon initiation or cessation of drug treatment,

vii

INTRODUCTION

The gradient of inhibition during a post- discrimination generalization test (Jenkins and Harrison,19 62) represents the degree of control over behavior exerted by a stimulus correlated with extinction during prior discrimination training. As the test stimuli grow more dissimilar to the S- the degree of generalization of inhibitory control from S- to those stimuli decreases, and more responding occurs. Thus, greater differential responding to novel stimuli from the same dimension as S- presented during the generalization test in extinction implies greater inhibitory control by the S-.

If during the preceding discrimination training the stimulus correlated with reinforcement (S+)„ and presented successively with the S- is from the same dimension as S-, the modal response rate during generalization testing will occur not to the S+ but to a novel test stimulus farther removed from the S- (Hanson, 1959). This change in the gradient of generalization, "peak shift," is considered (Terrace, 1966; 1972) to be a direct reflection of theinhibitory properties of the S-.

■ ' ' - • .Both of these indices of the inhibitory stimulus

control of an appetitively motivated operant response, i.e,, the gradient of inhibition and the peak shift, have

been studied and defined in the context of the generaliza­tion test in extinction following two-stimulus discrimina­tion training. Only a few studies (Reynolds, 1961b;Honig and Slivka, 1964; Martin, Sczerzenie, and Lyons, n.d.1 have suggested that the same process may also affect behavior during the discrimination training itself if more than two stimuli from the same dimension ■ are presented to the organism. The presentation of asingle S- in sequence with multiple S+'s will result in differential responding to those S+'s in accord with their dimensional relation to the S- even though all S+'s are correlated with equal reinforcement schedules. This paradigm provides a method of examining the process of generalization of inhibition during the acquisition and maintenance of an appetitively motivated discriminative response.

It is within this context that the present experi-9ment sought to establish the effect of -A trans-

9tetrahydrocannabinol (A THG) on learning and inhibitory9stimulus control, Previous research with A TEC, the major

psychoactive component of marijuana, in the area of operant conditioning has indicated a biphasic dose-response rela-

9tionship between acutely administered A TRC and rate of response maintained by intermittent schedules of reinforce­ment (Grisham and Ferraro, 1972). Studies of response rate under chronic A THC administration have indicated a rapid

appearance of tolerance to its rate suppressing effects at high doses and to its stimulant effect at low doses (Frankenheim, McMillan, and Harris, 1971; Ferraro and Grisham, 1972)„ A complex learned behavior, delayed matching to sample by chimpanzees, was disrupted by A^THC with delay intervals of zero or greater while simultaneous matching was not affected (Ferraro, Grilly, and Grisham, 1974), This indicates that the drug affects short term memory but not perceptual processes or performance of a well learned task. Tolerance to this disruptive effect of A^THC occurred at short delay intervals.

QThe effect of A THC during the acquisition of an appetitively motivated operant discrimination has recently been studied in monkeys and rats. No effect on the rate of acquisition was found with either monkeys on the initial learning of a simultaneous color discrimination (Gluck, Ferraro, and Marriott, 1973), or with rats on the acquisi­tion of a successive discrimination with auditory cues (Fetterolf and Ferraro, 197 4a). Effects on avoidance acquisition (Barry and Kubena, 1971; Gonzales and Carlini, 1971) and maze learning (Henriksson and Jarbe, 1971) have been inconsistent. In both studies on avoidance learning, however, there was evidence that removal of the drug produced a short term decrement in performance, Disruption of the performance of chimpanzees on the match to sample task also occurred for the first few sessions following drug

removal. This effect on an established discrimination by a change in drug state has been supported by recent work with rats trained on a three stimulus auditory discrimination.A 2.0 mg/kg dose given acutely disrupted discrimination accuracy by differentially increasing responding in S- (Fetterolf and Ferraro, 1974b), although this same dose chronically administered had no effect on the acquisition of a similar discrimination. The former finding conflicts with earlier work from the same, lab on successive and simul­taneous discrimination in primates. Accuracy of performance was not affected in that species by acute administrations of A^THC over a wide range of doses (Ferraro, Gluck, Fetterolf, and Marriott, 1974).

Studies of the effects of A^THC on stimulusgeneralization have been few. Lyons, Ferraro, Lyons,Sullivan, and Downey (1973) have demonstrated an enhancementof the peak shift in post-discrimination generalizationgradients in rats trained on a floor tilt discrimination.In that study the increase in relative response rate to the

9peak shift stimulus was directly related to A THC dose. It was concluded that the enhanced peak shift reflected an incremental effect of the drug on inhibitory control by S-. This interpretation has been substantiated by the results of a discrimination reversal learning experiment with primates in which, as mentioned above, acquisition was not affected but reversal learning was retarded by chronic administration

qof A THC (Gluck et al., 1973)„ The authors discuss thepossibility that this detrimental effect of the drug may bemediated by enhancement or preseveration of the inhibitoryproperties of the S-. The findings of Lyons et al. (1973)are in conflict with those of Marriott and Ferraro (1974)who, after establishing a baseline response rate to 11 lineangle stimuli, trained pigeons on a discrimination with avertical line as S- and absence of line as S+. Generaliza-

9tion testing under a .07 5 mg/kg dose of A THC revealed no effect on inhibitory stimulus control although response output was reduced. The differences in procedure of the two studies, most notably the pretraining with the generaliza­tion test stimuli in the Marriott and Ferraro (1974) study,do not permit a direct comparison of the results. The

9question concerning the effect of A THC on inhibitory stimulus control is thus left unanswered,

The present experiment was designed to assess the9effects of chronic A THC administration on the acquisition

of an appetitively motivated complex discrimination in pigeons and on the maintenance of that same behavior acquired in the absence of the drug. In addition, the multiple stimulus task, establishing an central on the dimension of wavelength to four S+'s provided a means of observing the drug’s effect on the development and maintenance of inhibitory stimulus control„ The drug effect on both stages of discrimination was assessed by

means of a counterbalanced design of 20 drug and 20 controltreatment sessions within 4 0 sessions of discriminationtraining. According to the Lyons et al„ (1973) study the

9administration of A THC to subjects at an asymptotic levelof discrimination performance, as were their subjects priorto generalization testing, would enhance inhibitory controlby the S- and, therefore, any differential rate of responsein the presence of the S+'s„ This differential effectshould be seen in addition to an overall rate increase

9expected under the low dose of A THC used. It might also be expected that removal of the drug from those subjects receiving it during the acquisition phase, and initiation of drug administration to those acquiring the discrimination without the drug would result in a temporary disruption of performance.

'Another aspect of discrimination learning which may be affected by the drug is behavioral contrast. No previous research has explicitly dealt with this phenomenon in con-

9junction with A THC. Behavioral contrast refers to an increase during discrimination training of response rate in the presence of stimuli signaling, the relatively more dense schedule of reinforcement (Reynolds, 1961a). This rate increase is often correlated with a response rate decrease in the presence of stimuli correlated with the less dense reinforcement schedule. The decrement in responding under one component of the discrimination, however, has been shown

not to be a necessary condition (Nevin and Shettleworth, 1966). Due to the' correlation between the appearance of behavioral contrast and the occurrence of other phenomenon such as peak shift and gradients of inhibition in the same experimental Subjects, contrast has been interpreted as reflecting the inhibitory properties of the less densely reinforced stimulus (Terrace, 1966; 1972). If so, an enhancement of the effect may occur under the drug, An enhancement due to a drug induced increase in the inhibitory properties of the S- could be distinguished in the present experiment from one due to a magnification of the change in relative reinforcement density under S+. In the former case, a change in the shape of the inhibitory gradient would be expected to occur both between S- and the stimuli near to it on the dimension of wavelength (proximal stimuli) and between those stimuli and the two dimensionally more distant S+1s (distal stimuli) (Martin et al„, n.d.). To support the latter interpretation, an equal enhancement of response rate must occur in the presence of both proximal and distal stimuli« This sort of change would not be distinguishable from an overall rate increase to S+ which has often occurred in previous studies

qinvolving A TEC and discrimination performance (Ferraro et a l , 197 4). .

In order to assess the drug effect during acquisi­tion and performance of both an easy and a difficult

discrimination task, the number of times the S- was presented within a training session was varied. It was assumed that the occurrence of S- a greater number of times per session would constitute an easier discrimination. Also, if the strength of the inhibitory properties of adiscriminative stimulus is a function of its frequency of

\occurrence in conjunction with non-reinforcement, as is suggested by the gradual decline of response rate during extinction and the correlated gradual development of behavioral contrast, then the influence of the drug is being assessed with respect to behavior under control of dis­criminative stimuli of differing inhibitory value.

METHODS

SubjectsSixteen, experimentally naive White King pigeons

were used as subjects. Four of the birds died before completing the three training phases and the data from only one of those will be considered. The subjects were obtained from a local supplier and maintained throughout the experiment at 7 0 to 75 per cent of their free feeding weight.

Apparatus. The subjects were trained in four, operant pigeon

chambers (11" by 11" by 13-1/2"; Grason Stadler Model 110.OPE) each containing a single response key. The key> mounted behind a 3/4" circular aperture, could be transilluminated with various wavelengths of light pro­vided by Industrial Electronic Engineers On-line Display Cells (Models E4580-164 and E4580—184). The colors of light used as stimuli, 538, 548, 555, 566, and 576 nm, were not monochromatic and were considered to be on an ordinal scale (Lyons and Klipec, 1971).

The response key was mounted in the front panel of the chamber three inches above a two by one and three-­quarter inch opening which provided access to a grain

hopper. The hopper was raised for three seconds when a programmed reinforcement circuit was completed. Stimulus presentations, reinforcement and response recording were controlled by automatic programming equipment. In the upper right of the panel containing the response key, a white houselight was mounted behind a plastic disc and was illuminated during stimulus presentations. Fans mounted in each chamber provided masking noise and ventilation.

ProcedureAll subjects upon arriving at the laboratory were

individually caged and allowed free access to mixed grain and water until reaching a stable, free feeding weight.Each pigeon was then reduced to between 7 0-75% of its free feeding weight and maintained at the reduced weight by controlled feeding„

Each subject was magazine trained, conditioned to key peck and then allowed to earn 50 reinforcements on a continuous reinforcement (CRF) schedule on three consecutive days. This CRF training was followed by training with three diminishing densities of reinforcement: one half session, 20 stimulus presentations, with variable interval (VI) 15 second; one session, 40 stimulus presentations, with VI 30 second, and one with VI 60. second (VI 1) . During key peck and CRF training the key was illuminated with white light. During the sessions when the reinforcement schedule

11was being reduced and for the remainder of the experiment, the five stimuli were presented in a quasi-random sequence. Each stimulus was presented for 50 seconds followed by a ten second blackout of the response key and houselight.

An outline of procedures for the remainder of the experiment appears in Table 1. Following key peck and schedule training all subjects were given 25 sessions of non-differential training (NDT I) with VI 1 reinforcement scheduled during the presentations of all five stimuli.Half of the subjects received an equal number, which constituted the difficult task (Group D), of presentations of each stimulus during a session. The remaining subjects received 20 presentations of the 555 ran stimulus and five presentations of each of the other stimuli, the easier task (Group E), during training« The NDT I phase was included to establish a stable level of response rate to the five stimuli against which the effects of discrimination training could be viewed.

Discrimination training (DT) consisted of 40 sessions during which VI 1 reinforcement continued in the presence of the 538, 548, 566, and 576 nm stimuli while extinction was Scheduled in conjunction with the 555 nm stimulus. For DT the subjects were assigned to the different drug groups. Groups D and E were divided evenly: half of each, being injected with control solution CO group), throughout DT; the rest receiving control injections before 20 consecutive

Table 1» Outline of drug and training procedures»

. Drug conditions A^THC ' , -

Group Subject Task difficulty

NDT I: VI 1 - all

stimuli

DT: EXT- 555 nm only;

. days 1-20

VI 1 -other stimuli

days 21-40NDT II

VI 1 - all stimuli

0 r- D A - 8 A -r 15

8 S- (555 nm) per session

0.0 mg/kg (Tween-80 in saline)

0.0 mg/kg

0 T E A T 3 C -r 5

20 S-r per session

No Drug No Drug, 25 r- D Z 2 8 S™ per .25 mg/kg 0.0 mg/kg

session■ Z - 8

Z - 4 0.0 mg/kg .25 mg/kgZ ? 6

.25 - E Z - 1 20 per .25 mg/kg 0.0 mg/kgsession

Z f 26Z T 5 0.0 mg/kg .25 mg/kg

13sessions and drug injections before 20 consecutive sessions (.25 group). Half of the subjects in each of Groups .25 D and .25 E received the control series on days one through20 of discrimination training and the drug series on days21 through 40. The remaining subjects received the control and drug series in the reverse order.

9The drug, A THC, was suspended at a concentration . of .25 mg/cc in a solution of Tween-80 in saline (4% vol/ vol) and administered at a dose of .25 mg/kg. Control injections were of an equivalent volume of the Tween-8 0 solution (0.0 mg/kg). All injections were intramuscular and were given two hours prior to a training session,While the subjects were receiving control or drug injections (i.e./ during DT) training sessions were held every other day,

DT was followed by 25 days of non-differential training (NDT II) which were similar in procedure to those of NDT I. This constituted a return to baseline procedure to determine whether the original pre^discrimination train­ing and prer-drug response rates would be reestablished.

RESULTS

Response rates in the presence of each stimulus during the forty days of DT were divided by their respec­tive baseline rates and are plotted as a function of sessions in Figures 1, 2, 3, and 4. The mean response rate over the last five sessions for NDT I for each stimulus was taken as each subject's baseline rate. Responding in S+ in the figures is presented as averages of the relative rates to the two distal stimuli and to the two proximal stimuli. A criterion of S- rate falling at or below »5 of baseline for three consecutive days was used in assessing discrimination performance.

There was no consistent pattern of performance within any of the experimental groups during DT. The performances of drug birds (Groups .25-D and E) in general did not differ from that of the non-drug birds (Groups0-D and E). According to the discrimination criterion, only two of the Group 0 birds, whose graphs are shown in the lower panels of Figures 1-4, learned the discrimination bird C-5 (Figure 2) , Group 0-E and bird A-8 (Figure 3) , Group 0-D. Bird A-3 (Figure 1) Group O-KE, showed con­sistent differential responding although its S- response rate did not meet the criterion. Recall that all of these birds received only Tween solution injections throughout DT

RES

PON

SES

- PR

OPO

RTI

ON

OF

B

AS

EL

INE

15

555(S~)SESSION RATE 5 5 5 B A S E L I N E RATE 5 4 8 + 5 66 RATES/ 2 (SESSION)

3.0 ZIh b(AfTHC-TWEEN) 5 4 8 + 5 66 R A T ES / 2 ( BA SE L I N E )

5 38 + 5 7 6 RATES/2 (SESSION) 5 3 8 + 5 7 6 R AT E S / 2 (BASELINE)20

0.0 20 30 4 0_ Z5 2Or ne

(TWEEN-A9 THC)0-0

00 20 30 4 0

3.0 A3I B(TWEEN-TWEEN)

2.0

0.0 20SESSIONS

Figure 1. Relative response rates to distal, proximal and S- stimuli as a function of sessions during discrimination training for Group E: Z-l, Z-5 and A-3.

RESP

ONSE

S -

PROP

ORTI

ON

OF

BA

SELI

NE

Z 26<o r 118{£? THC-TWEEN)

3.0

2.0

1.0

00 4020 30

40 1-7HB(TWEEN-A9THC)

3.0

2.0

10

0.0 20 30 40

40r C-5 IB(TWEEN-TWEEN)

3.0

20

I 0

00 4020SESSIONS

30

Figure 2. Relative response rates to distal, proximal and S- stimuli as a function of sessions during dis crimination training for Group E: Z-26, Z-7 and C-5,

RE

SP

ON

SE

S-

PRO

POR

TIO

N

OF

BA

SE

LIN

E

4 0h a( £ ? THC-TWEEN)

30

2.0

1.0

00 4 0302040 r 2-4

H A(TWEEN-A9 THC)

3.0

2.0

0.0 1 '---------A -8

2 0 r 1AI (TWEEN-TWEEN)

3020 4 0

p-

1.0

0.0 3020SESSIONS

40

Figure 3. Relative response rates to distal, proximal and S- stimuli as a function of sessions during dis crimination training for Group D : Z-2, Z-4 and A-8,

RE

SP

ON

SE

S-P

RO

PO

RTI

ON

OF

B

AS

EL

INE

18

4 0 " Z -8 h a(A9THC-TWEEN)

20

1.0

0.0 4 030203Or- z-6

H A(TWEEN-A9 THC)

2.0b - ft - O »

10

00 4030203 0 A-15

I A(TWEEN-TWEEN)

2 0

P -

10

0.0 20SESSIONS

30 40

Figure 4. Relative response rates to distal, proximal and S- stimuli as a function of sessions during dis crimination training for Group D: Z-8, Z-6 and A-15.

19From an examination of differential responding to the S+ stimuli among these Group 0 subjects it can be seen that one bird (C-5, Figure 2) meeting the discrimination criterion showed a distal stimulus response rate consistently elevated above that to the proximal stimuli. This differ­ential responding was less consistent during the second half of DT. Although not displaying criterion suppression of rate to S-, bird A-3 (Figure 1) also consistently responded more in the presence of the distal than the proximal S+ stimuli. Bird A-8 (Figure 3) which learned the discrimina­tion showed no tendency to differentiate between the S+ stimuli. Bird A-15 (Figure 4, Group 0-D) displayed extreme variability inx response rate to all stimuli across all training days. Birds A-3, C-5 and A-8 (Figures 1-3, respectively) showed an increase in overall S+ rate over baseline (ordinate =1.00) concurrent with their declining response rates in the presence of S-.

Of the four birds of Group .25 which received the drug for the first 20 sessions of DT (top panels of Figures1-4), only one (Z-26, Figure 2: Group ,25-E) met the dis­crimination criterion while under the drug. The remaining birds showed either no rate differentiation in the presence of any stimulus (Z-2, Figure 3: Group .25-D), or an almost complete generalization of response rate suppression from S- to the proximal S+ stimuli (Z-l, Group ,25-E and Z^8, Group ,25-D; Figures 1 and 4, respectively!. Each of these

20response patterns is seen also in the Group II birds receiving control injections at this time (middle panels . of Figures 1-4): Z-7 (Figure 2) showing discrimination;Z—4 and Z-6 (.Figures 3 and 4) showing no discrimination, and Z-5 (Figure 1) showing no discrimination between S- and proximal S+ stimuli„ There was a transient rate decrease in only two out of four of the birds receiving drug at the beginning of training (Z-2, Figure 3 and Z-2 6, Figure 2).

After the first 20 days of discrimination training,the drug regimen of the Group .25 birds was switched from9 9A THC to Tween injections or from Tween to A THC injections.

Neither change resulted in a consistent alteration of per­formance during the initial sessions of this second half of DT. Also, the continuation of drug treatment or control treatment over the last .20 training sessions produced no observable change from the variable performances of the first 20 sessions.

DISCUSSIONI

The absence of consistent performance across thesubjects of any group in the present experiment allows noconclusions concerning the effect of A^THC on multiplestimulus discrimination learning in pigeons. One pointshould be made, however, concerning a lack of effect on thepattern of responding peculiar to each bird. That is, in no

9case did the withdrawal or initiation of A THC injectionsmarkedly alter the performance of any subject. For birdsshowing some differentiation of response rate among thestimuli, no radical change in the relative rates occurredfollowing the change in drug state. This is in contrast toprevious findings of disruption of operant performance uponpresentation or withdrawal of the drug (Barry and Kubena,1971; Gonzales and Carlini, 1971; Fetterolf and Ferraro,197 4b). Also, the drug produced no consistent enhancementor suppression of response rate.

In order to explain the variability in performance9which obviated any conclusions concerning A THC effect, an

examination of control group performance is necessary.Birds in Group 0 and those in Group .25 receiving A^THC injections during the second half of DT are more variable in their performance of the discrimination than were the subjects from a previous study using the same discrimination

paradigm (Martin et al., n,d,[. In that study a decline in rate was consistent across all sub'jects and was accompanied by an increase in proximal stimulus rate with a concurrent, greater increase in distal stimulus rate. This comparison suggests that the control procedure itself, intramuscular injection of the Tween solution, may have disrupted acquisition of the discrimination. The procedure of holding DT sessions every second day was instituted early in the course of the experiment in order to ameliorate the observed debilitating effect of continued injection.

When superimposed upon this variability, then, the .9effect of such a low dose of A THC may have been over^

shadowed, Other work in this lab has demonstrated that .25 mg/kg does produce a discriminable state in pigeons (Lyons and Akins, in preparation) in that when it is associated with one component of a multiple reinforcement schedule the dose level of the drug can gain stimulus control over operant performance. The dose used in the Fetterolf and Ferraro (1974b) study, 2.0 mg/kg in rats, which produced a differential increase in S- responding may be considered a relatively low dose although not equivalent to a .25 mg/kg dose in pigeons on the basis of the changes in operant response rates produced by these doses in the two species (Frankenheim et al., 1971). Therefore, the lack of effect in the present experiment may have resulted from the extreme variability produced by the underlying control

23treatment in the beginning of DT, the length of trainingpreceding drug administration during the second half of DTor a species difference with respect to the threshold for

9disruptive properties of low A THC doses. The data do notpermit a firm statement on this point.

Further research in the area of the effects of 9chronic A THC administration on stimulus control is needed.

It is suggested by the results of the present experiment, however, that the drug vehicle control procedures which are required must be designed so as to not in themselves produce marked changes in the behavior under study. It will be

9possible to assess the effects of low doses of A THC only against such a stable baseline. Since it appears that continuous injection increased the variability of per­formance, perhaps reducing the number of injections over time would result in more stable behavior. For example, the Fetterolf and Ferraro (1974b) study used a design in which two days of drug injection were separated by training days with no injection. This allowed observation of the development of tolerance to the drug dose, the drug effect itself and the course of recovery from those effects during the non-injection days.

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Barry, H., III, and Kubena, R. K . Repeated high doses ofA -tetrahydrocannabinol enhance acquisition of shock avoidance by rats. Proceedings of the American Psychological Association, 1971, 6, 747-748.

Ferraro, D. P., Gluck, J. P., Fetterolf, D. J., and Marriott, R. G, Interactions between drugs and the stimulus control of behavior. In R. Stretch (Ed.),Behavioral models of drug dependence, 1974.

Ferraro, D. P., Grilly, D. M., and Grisham, M. G. A^- tetrahydrocannabinol and delayed matching-to- sample in chimpanzees. In J. M. Singh (Ed.),Drug addiction: Vol. III. New York: Futura,1974.

Ferraro, D . P., and Grisham, M. G. Tolerance to thebehavioral effects of marijuana in chimpanzees. Physiology and Behavior, 1972, 9, 49-54.

9Fetterolf, D, J., and Ferraro, D. P. Effects of A ^ tetrahydrocannabinol on the acquisition of a successive discrimination in rats. Paper presented at the Southwestern Psychological Association Meeting, El Paso, 1974a.

9Fetterolf, D. J., and Ferraro, D. P. Effects of A ^tetrahydrocannabinol on the successive discrimina^ tion performance of rats. Paper presented at the Rocky Mountain Psychological Association Meeting, Denver, 197 4b.

Frankenheim, J. M., McMillan, D. E., and Harris, L. S.Effects of 1-A^- and 1-A -trans-tetrahydrocannabinol and cannabinol on schedule-controlled behavior of pigeons and rats. Journal of Pharmacological and Experimental Therapeutics, 1971, 17 8, 241^252.

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25Gluck, J. P., Ferraro, D. P., and Marriott, R. G. Retarda­

tion of discrimination reversal by A^- tetrahydrocannabinol in monkeysv Pharmacology Biochemistry and Behavior, 1973, 1, 605-608.

Gonzales, S. C ., and Carlini, E . A. Extinction of operant responses by rats under the effects of Cannabis sativa extract. Psychonomic Science, 1971, 24, 203-204.

Grisham, M. G., and Ferraro, D. P. Biphasic effects ofA^-tetrahydrocannabinol on variable interval schedu schedule performance in rats. Psychopharmacologia,• 1972, 27, 163-169.

Hanson, H. M. Effects of discrimination training onstimulus generalization. Journal of Experimental Psychology, 1959,51,7 9-88.

Henriksson, B. G., and Jarbe, T. The effect of two tetrahydrocannabinols (A -TEC and A^-THC) on conditioned avoidance learning in rats and its transfer to normal state conditions, Psychopharmacologia, 1971, 22, 23-̂ 30.

Honig, W. K., and Slivka, R. M. Stimulus generalization of the effects of punishment. Journal of the Experimental Analysis of Behavior, 1964, 7, 21^25.

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