Behavioral Effects in Monkeys of Racemates of Two Biologically Active Marijuana Constituents

Scheckel, Carl L.; Boff, Edward; Dahlen, Philip; Smart, Terrence

doi:10.1126/science.160.3835.1467

Science

1968

DOI: 10.1126/science.160.3835.1467

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Behavioral Effects in Monkeys of Racemates of Two Biologically Active Marijuana Constituents

Carl L. Scheckel

Edward Boff

Philip Dahlen

et al.

Abstract: Both dl-Delta(8)- and dl-Delta(9)-tetrahydrocannabinol produced marked alterations of behavior in rhesus and squirrel monkeys. Squirrel monkeys appeared to have visual hallucinations. Continuous avoidance behavior of squirrel monkeys was stimulated by both drugs, but high doses of dl-Delta(9)-tetrahydrocannabinol also caused depression after the stimulant phase. Complex behavior involving memory and visual discrimination in rhesus monkeys was markedly disrupted by both drugs.

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Cited by 113 publications

(21 citation statements)

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“…We observed a 50% decline in brain levels after 1 week following an intraperitoneal injection. This represents an appreciable amount present after 1 week and may partially explain the long lasting effects of THC in monkeys as shown by Scheckel, Boff, Dahlem & Smart (1968). Our results are in contrast to those of Ho, Fritchie, Kralik, Englert, McIsaac & Idanpaan-Heikkila (1970) who found that following the administration of 3H-THC by inhalation there was less than a 25% decline in brain levels after 1 week.…”

contrasting

confidence: 92%

Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Layman

Milton

1971

British J Pharmacology

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contrasting

confidence: 92%

Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Layman

Milton

1971

British J Pharmacology

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“…For both drugs, Copyright 1986 Psychonomic Society, Inc.the higher doses produced an increase in response failures. A similar pattern of results was found in a later study by Scheckel, Boff, Dahlen, and Smart (1968), who administered A 9 -THC (dose range of 0.25-4.0 mg/kg) to monkeys. As the dose increased, there was a decrease in the limit of delay and an increase in the number of response failures.…”

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confidence: 86%

The use of the titrating delayed matching-to-sample procedure for analyzing drug effects

Woodward

Watson

Blampied

et al. 1986

Bull. Psychon. Soc.

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A titrating delayed matching-to-sample (TDMTS) procedure, in which the delay between the sample and comparison stimuli depends on the subject's performance, was used to assess the effects of 0.5 mg/kg of haloperidol in pigeons. The results showed that the decrease in the limit of delay sustained by the subjects in the drug condition could not be attributed to drug effects on short-term memory, because the limit of delay measure was confounded by the effect of the drug on psychomotor responding. Implications of the use of the TDMTS procedure are discussed.Matching-to-sample (MTS) is an experimental procedure that has been used to assess the effects of drugs on stimulus control. In MTS, a trial begins with the presentation of a sample stimulus. After an appropriate response is made, two or more comparison stimuli are presented, one of which is identical to the sample stimulus. To obtain a reinforcer, the subject must respond to the comparison stimulus that' 'matches the sample" (McMillan, 1981).When a delay is interpolated between the sample and comparison stimuli (delayed matching-to-sample, DMTS), the procedure becomes useful for the study of both concept formation and short-tenn memory (STM) in animals (McMillan, 1981). The DMTS paradigm has two advantages in the study of STM. First, it minimizes the influence of peripheral mediating responses, and second, DMTS tasks may employ exteroceptive stimuli that permit a rigorous manipulation of stimulus parameters and precise specification of stimulus and retention interval duration (Pontecorvo, 1983).Perfonnance under DMTS, across a variety of species, shows that with increases in the delay interval, there is a corresponding decrease in the accuracy of the animals' perfonnance. Thompson (1978) has suggested that DMTS might be more sensitive to drug effects than is MTS because DMTS is presumably under weaker control by the sample stimulus. Stimulus control by the sample stimulus should weaken progressively as the delay increases. Therefore, under DMTS, drug effects might be seen at This report is based on data from a project submitted by the first author in partial fulfillment of the requirements for a master's degree in psychology. The authors acknowledge the assistance of the following pe0-ple: Chris van Halewyn for writing the computer program, Ijan Beveridge for his care of the animals, and Robin Phillips for his assistance in the preparation of this manuscript. Requests for reprints should be addressed to L. Woodward, Department of Psychology, University of Canterbury, Christchurch, New Zealand. doses lower than those at which effects appear under MTS, or larger drug effects may be seen at the same dose as the delay increases (McMillan, 1981). The DMTS procedure has proved useful in the assessment of the effects of a variety of drugs (Heise & Milar, 1984;Thompson, 1978).In the standard DMTS procedure, the delay values at which the subjects work are usually arbitrarily set by the experimenter. One variation of the DMTS procedure is the titrating DMTS procedure (TD...

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“…During some sessions, however, administration of A9THC did increase the rates of responding relative to the control rates of responding after Triton X 100. Similar rate increases during the FI component of a mult FI FR schedule have been observed after daily injections of morphine and methadone in pigeons (6), but rate increases have not been observed with pigeons for A9THC when injections were widely spaced during the determination of dose-effect curves (2), although rateincreasing effects of tetrahydrocannabinols also have been observed in monkeys when shock-avoidance procedures were used (10).…”

mentioning

confidence: 77%

Many Responses per Food Reward with Free Food Present

Neuringer¹

1970

Science

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mg/kg, the rates of responding under the Fl component were within the control range. During subsequent sessions, as the dose was increased to 20 times the original dose, rates of responding fell below those of controls infrequently. During some sessions, however, administration of A9THC did increase the rates of responding relative to the control rates of responding after Triton X 100. Similar rate increases during the FI component of a mult FI FR schedule have been observed after daily injections of morphine and methadone in pigeons (6), but rate increases have not been observed with pigeons for A9THC when injections were widely spaced during the determination of dose-effect curves (2), although rateincreasing effects of tetrahydrocannabinols also have been observed in monkeys when shock-avoidance procedures were used (10).Doses of A9THC of 10 mg/kg or higher were given for 8 days after the 28 days shown in Figs. 1 and 2, and then adminuistration was discontinued.Although small changes in the rates of responding were observed when the drug was withdrawn, no gross behavioral symptoms suggesting a withdrawal syndrome could be detected, nor did the general health of the pigeons seem to be impaired during or after longterm administration. Bird 6512 was given 10 mg/kg (from the same sample of A9THC used previously) after 4 weeks during which no injections were given. Much of the tolerance to this dose had disappeared during the 4-week period, since bird 6512 responded at a rate of 0.07 response per second during the FI component and at a rate of 0.18 response per second during the FR component.During the course of these experiments, the purity of the A9THC was established both by gas chromatography and by injections of the solutions used into birds (6640 and 5117) that had not previously received A9THC. Table 1 shows the effects of 5.6 mg/kg in bird 6640. The injection was drawn from the same sample used to inject the two pigeons in the tolerance study.The table shows that the 5.6 mg/kg dose, which did not decrease responding under either schedule component in the tolerant birds, completely eliminated the responding of bird 6640 2 hours after injection, and effects could still be seen 48 hours after injection. In -another experiment, a dose of 36 mg/kg was given to bird 5117. Within 31 JULY 1970 2 hours this bird could not stand, walk, or fly normally and refused food. At 8 hours after the injection, the bird lay on the cage floor with labored respiration. The bird did not stand up until 48 hours after the injection, and he did not eat until 72 hours after the injection. Yet this dose (36 mg/kg) had no effect on schedule-controlled behavior in the tolerant birds.Our experiments demonstrated that a dose of A9THC which completely disrupts food-reinforced responding in pigeons for many hours can be increased more than 20-fold without disrupting this schedule-controlled behavior in tolerant birds. Since no behavioral effect was obtained at this very large dose, the 20-fold increase probably does not represent the lim...

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Behavioral Effects in Monkeys of Racemates of Two Biologically Active Marijuana Constituents

Cited by 113 publications

References 9 publications

Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

The use of the titrating delayed matching-to-sample procedure for analyzing drug effects

Many Responses per Food Reward with Free Food Present

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Behavioral Effects in Monkeys of Racemates of Two Biologically Active Marijuana Constituents

Cited by 113 publications

References 9 publications

Distribution of tritium labelled Δ1‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Distribution of tritium labelled Δ1‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

The use of the titrating delayed matching-to-sample procedure for analyzing drug effects

Many Responses per Food Reward with Free Food Present

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Product

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Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration

Distribution of tritium labelled Δ¹‐tetrahydrocannabinol in the rat brain following intraperitoneal administration