Failure of Δ9-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys

Rs, Mansbach; Kl, Nicholson; Br, Martin; Rl, Balster

doi:10.1097/00008877-199404000-00014

Cited by 99 publications

(67 citation statements)

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“…Although there are many variations to this basic experimental procedure, a commonly used method for assessing the reinforcing efficacy of a test drug in experimental animals is to compare self-administration of the drug to self-administration of a standard drug of known abuse potential and to a vehicle control in the same subject (e.g., Johanson and Balster, 1978;Bergman and Johanson, 1985;Tanda et al, 2000). These studies are usually performed in rhesus monkeys (Macaca mulatta), squirrel monkeys (Saimiri sciureus) or rats that have learned to self-administer a prototypical drug of abuse, such as cocaine or codeine, under a schedule requiring a fixed number of responses to obtain each injection (e.g., a 10-response, fixed-ratio schedule of drug injection, FR10) (Goldberg et al, 1971;Goldberg, 1973;Marquis et al, 1989;Mansbach et al, 1994;Tanda et al, 2000). The drugs to be tested are then substituted for the training drug and evaluated for their ability to maintain levels of responding greater than those maintained during vehicle substitution.…”

Section: Evaluation Of the Reinforcing Effects Of Thc And Other Synthmentioning

confidence: 99%

“…Over the last three decades, many attempts to demonstrate intravenous self-administration of THC or of synthetic cannabinoid CB 1 receptor agonists by experimental animals were relatively unsuccessful (Pickens et al, 1973;Kaymakcalan, 1973;Harris et al, 1974;Carney et al, 1977;van Ree et al, 1978;Mansbach et al, 1994) (Table 1). None of these studies clearly demonstrated persistent, dose-related, self-administration behavior maintained by THC or synthetic cannabinoids, which would be susceptible to vehicle extinction and subsequent reinstatement in the absence of unusual "foreign" conditions.…”

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

“…Also, chronic diet restriction (rats were maintained at 80% of their normal body weight) was a necessary condition in this study by Fattore and colleagues (2001), since rats on an unrestricted diet did not acquire cannabinoid selfadministration behavior. The synthetic cannabinoid CB 1 receptor agonist CP 55, 940 has not yet been reported to be self-administered intravenously by experimental animals (e.g., Mansbach et al, 1994), but it has been reported to maintain self-administration behavior of rats when injected intracerebroventricularly (Braida et al, 2001b). Finally, self-administration behavior is not maintained by cannabinoid receptor antagonists in experimental animals (Beardsley et al, 2002) (Table 1).…”

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

“…A potential explanation for these observed effects is that ketamine and dextrorphan share some discriminative-stimulus effects (Holtzman, 1980;Herling et al, 1981), as do diazepam and pentobarbital (Colpaert et al, 1976;Shannon and Herling, 1983). However, attempts to directly substitute THC for drugs thought to have some discriminative-stimulus effects in common with THC (such as phencyclidine, phenobarbital or ethanol) have been unsuccessful in generating THC self-administration behavior (Harris et al, 1974;Mansbach et al, 1994).…”

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

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Self-administration of cannabinoids by experimental animals and human marijuana smokers

Justinová

Goldberg

Heishman

2005

Pharmacology Biochemistry and Behavior

116

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Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drugnaïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB 1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans.

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Section: Evaluation Of the Reinforcing Effects Of Thc And Other Synthmentioning

confidence: 99%

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

See 2 more Smart Citations

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Justinová

Goldberg

Heishman

2005

Pharmacology Biochemistry and Behavior

116

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“…Although several groups have reported that cannabinoids produce a robust conditioned place preference (Braida et al, 2001a;Lepore et al, 1995;Valjent and Maldonado, 2000) others have reported that cannabinoids produce a conditioned place aversion (Parker and Gilles, 1995;McGregor et al, 1996;Sañudo-Pena et al, 1997). Although it has been reported that both the cannabinoid receptor agonists, WIN 55212-2 and CP55940, are self-administered by mice, an effect that is blocked by pretreatment with a CB 1 receptor antagonist rimonabant (Braida et al, 2001b;Ledent et al, 1999;Martellotta et al, 1998), there are several instances in which a failure of cannabinoid self-administration has been reported (Mansbach et al, 1994;Takahashi and Singer, 1981) . Cannabinoid receptor agonists, at low and pharmacologically meaningful doses, enhance electrical brain stimulation reward (Gardner et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward

Rademacher

Hillard

2007

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Since endocannabinoids modulate reward processing and the stress response, we tested the hypothesis that endocannabinoids regulate stress-induced decreased sensitivity to natural reward. Restraint was used to produce stress-induced reductions in sucrose consumption and preference in male mice. Central cannabinoid receptor (CB 1 ) signaling was modulated pharmacologically prior to the application of stress. The preference for sucrose over water was significantly decreased in mice exposed to restraint. Treatment of mice with a cannabinoid receptor agonist (CP55940) or fatty acid amide hydrolase inhibitor (URB597) attenuated, while the CB 1 receptor antagonist/inverse agonist, rimonabant (SR141716), enhanced, stress-induced decreases in sucrose preference. These data are consistent with a tonically active, stress-inhibitory role for the CB 1 receptor. Mice treated with 10 daily episodes of restraint showed reduced sucrose preference that was unaffected by CP55940 and URB597. However, rimonabant produced a greater reduction in sucrose preference on day 10 compared to day 1. These data suggest that on day 10, endocannabinoid signaling is maximally activated and essential for reward sensitivity. The findings of the present study indicate that the CB 1 /endocannabinoid signaling system is an important allostatic mediator that both modulates the responses of mice to stress and is itself modulated by stress.

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The effect of a reduced energy diet and meal patterns on smoking and coffee drinking in women

Lawson¹,

Bulik²,

Rodefer³

et al. 1997

Int. J. Eat. Disord.

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Objective We examined the effect of three feeding conditions on cigarette smoking and coffee drinking in four healthy women. We hypothesized that food deprivation and changes in meal patterns would increase rates of smoking and coffee drinking based on extensive animal literature documenting this effect. Method: The conditions were: normal three meals per day containing usual energy intake, one meal per day (dinner time) containing 50% of usual energy intake, and three meals per day containing 50% of usual energy intake. Each condition lasted 3 days. Results: Neither reduction of energy intake nor alteration in the pattern of meals had any observable effect on number of cigarettes smoked, number of cups of coffee consumed, expired air carbon monoxide levels, or urges to smoke or drink coffee. Discussion: This study adds to the growing body of literature suggesting that the food deprivation effect observed in animals does not apply readily to humans. Reasons for the absence of this effect are discussed. © 1997 by John Wiley & Sons, Inc. Int J Eat Disord 21: 137–145, 1997.

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Failure of Δ9-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys

Cited by 99 publications

References 0 publications

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward

The effect of a reduced energy diet and meal patterns on smoking and coffee drinking in women

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