Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats

Wiley, Jenny L.; Barrett, RL; Lowe, John; Rl, Balster; Br, Martin

doi:10.1016/0028-3908(95)00027-4

Cited by 112 publications

(84 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with previous studies (Wiley et al, 1995), the potency of WIN55,212-2 was similar to that of THC, with a peak effect at an i.p. dose of 1 mg/mg.…”

Section: Effects Of Thc On Heroin Self-administration Under a Progressupporting

confidence: 90%

Cannabinoid Agonists but not Inhibitors of Endogenous Cannabinoid Transport or Metabolism Enhance the Reinforcing Efficacy of Heroin in Rats

Solinas

Panlilio

Tanda

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Accumulating evidence suggests that the endogenous cannabinoid system is involved in the reinforcing effects of heroin. In rats intravenously self-administering heroin, we investigated effects of cannabinoid CB 1 receptor agonists and compounds that block transport or metabolism of the endogenous cannabinoid anandamide. The natural cannnabinoid CB 1 receptor agonist delta-9-tetrahydrocannabinol (THC, 0.3-3 mg/kg i.p.) did not alter self-administration of heroin under a fixed-ratio one (FR1) schedule, except at a high 3 mg/kg dose which decreased heroin self-administration. Under a progressive-ratio schedule, however, THC dose-dependently increased the number of 50 mg/kg heroin injections self-administered per session and the maximal ratio completed (break-point), with peak increases at 1 mg/kg THC. In addition, 1 mg/kg THC increased break-points and injections self-administered over a wide range of heroin injection doses (25À100 mg/kg), indicating an increase in heroin's reinforcing efficacy and not its potency. The synthetic cannabinoid CB 1 receptor agonist WIN55,212-2 (0.3-3 mg/kg i.p.) had effects similar to THC under the progressive-ratio schedule. In contrast, AM-404 (1-10 mg/ kg i.p.), an inhibitor of transport of anandamide, and URB-597 (0.01-0.3 mg/kg i.p.), an inhibitor of the enzyme fatty acid amide hydrolase (FAAH) that degrades anandamide, or their combination, did not increase reinforcing efficacy of heroin at any dose tested. Thus, activation of cannabinoid CB 1 receptors facilitates the reinforcing efficacy of heroin and this appears to be mediated by interactions between cannabinoid CB 1 receptors and mu-opioid receptors and their signaling pathways, rather than by an opioid-induced release of endogenous cannabinoids.

show abstract

“…Consistent with previous studies (Wiley et al, 1995), the potency of WIN55,212-2 was similar to that of THC, with a peak effect at an i.p. dose of 1 mg/mg.…”

Section: Effects Of Thc On Heroin Self-administration Under a Progressupporting

confidence: 90%

Cannabinoid Agonists but not Inhibitors of Endogenous Cannabinoid Transport or Metabolism Enhance the Reinforcing Efficacy of Heroin in Rats

Solinas

Panlilio

Tanda

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…This pattern is the opposite of what would be expected had memory function been the primary factor involved in the cannabinoid modification of the nicotine CS. In addition, CP 55,940 effectively served as a S D indicating that it can acquire control over behavior (e.g., Wiley et al 1995a). Overall, we are led to the conclusion that at the dose used, and within the training conditions of the present research, CP 55,940 is not effective as a Pavlovian stimulus (i.e., a CS or positive feature).…”

Section: Discussionmentioning

confidence: 99%

“…The 0.01 mg/kg CP 55,940 is a relatively low dose in the cannabinoid literature (cf. De Vry and Jentzsch 2003;Wiley et al 1995a); a higher dose may be a more effective drug feature. Indeed, a weak discrimination developed when the training dose was increased to 0.03 mg/kg CP 55,940.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats

et al. 2009

View full text Add to dashboard Cite

Rationale -The cannabinoid CB 1 receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS). Objective -We examined the effects of rimonabant and the CB 1/2 receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature Materials and methods -Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003-0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions Results -Rimonabant blocked nicotine-evoked responding.CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task Conclusions -The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation.

show abstract

“…A protocol that we and others have used to characterize the abuse-related effects of cannabinoids is the two-lever choice drug discrimination procedure with THC or other cannabinoid CB1 agonists as the training drug (78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88). Rats or monkeys readily learn to discriminate even relatively low doses of THC from vehicle, although the development of stable discrimination performance usually requires 30 sessions or more.…”

Section: Discriminative Stimulus Effects Of Cannabinoidsmentioning

confidence: 99%

Endocannabinoid system involvement in brain reward processes related to drug abuse

Solinas

Yaşar

Goldberg

2007

Pharmacological Research

View full text Add to dashboard Cite

Cannabis is the most commonly abused illegal drug in the world and its main psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), produces rewarding effects in humans and non-human primates. Over the last several decades, an endogenous system comprised of cannabinoid receptors, endogenous ligands for these receptors and enzymes responsible for the synthesis and degradation of these endogenous cannabinoid ligands has been discovered and partly characterized. Experimental findings strongly suggest a major involvement of the endocannabinoid system in general brain reward functions and drug abuse. First, natural and synthetic cannabinoids and endocannabinoids can produce rewarding effects in humans and laboratory animals. Second, activation or blockade of the endogenous cannabinoid system has been shown to modulate the rewarding effects of noncannabinoid psychoactive drugs. Third, most abused drugs alter brain levels of endocannabinoids in the brain. In addition to reward functions, the endocannabinoid cannabinoid system appears to be involved in the ability of drugs and drug-related cues to reinstate drug-seeking behavior in animal models of relapse. Altogether, evidence points to the endocannadinoid system as a promising target for the development of medications for the treatment of drug abuse.

show abstract

Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats

Cited by 112 publications

References 13 publications

Cannabinoid Agonists but not Inhibitors of Endogenous Cannabinoid Transport or Metabolism Enhance the Reinforcing Efficacy of Heroin in Rats

Cannabinoid Agonists but not Inhibitors of Endogenous Cannabinoid Transport or Metabolism Enhance the Reinforcing Efficacy of Heroin in Rats

Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats

Endocannabinoid system involvement in brain reward processes related to drug abuse

Contact Info

Product

Resources

About