Endogenous cannabinoids as an aversive or counter-rewarding system in the rat

Sañudo-Peña, M.Clara; Tsou, Kang; Delay, Eugene R.; Hohman, Andrea G; Force, Michelle; Walker, J. Michael

doi:10.1016/s0304-3940(97)13424-3

Cited by 148 publications

(93 citation statements)

References 24 publications

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“…In our study, like others (McGregor et al, 1996;Sañudo-Peña et al, 1997;Chaperon et al, 1998), the cannabinoid agonist WIN 55,212-2 induced aversion in the CPP paradigm at all doses tested (0.4, 2.0, and 10.0 mg/kg) (Fig. 4).…”

Section: Discussionsupporting

confidence: 86%

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

López-Moreno

González-Cuevas²,

Fonseca³

et al. 2004

J. Neurosci.

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Section: Discussionsupporting

confidence: 86%

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

López-Moreno

González-Cuevas²,

Fonseca³

et al. 2004

J. Neurosci.

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“…Whereas most recreational users of cannabis experience a state of euphoria, others also report dysphoria and anxiety particularly at the beginning of cannabis consumption (Greg et al, 1976;Thomas, 1993;Grinspoon and Bakalar, 1997;Williamson and Evans, 2000). Human reports are in agreement with animal studies showing that D 9 -tetrahydrocannabinol (THC) and other synthetic cannabinoid agonists can induce both rewarding and aversive effects, as revealed in the place conditioned paradigm (Sañudo-Peña et al, 1997;Cheer et al, 2000;Valjent and Maldonado, 2000). The endogenous opioid system seems to play an important role in the different effects produced on the reward circuit after cannabinoid administration.…”

Section: Introductionmentioning

confidence: 74%

Involvement of κ/Dynorphin System in WIN 55,212-2 Self-Administration in Mice

Mendizábal

Zimmer

Maldonado

2005

Neuropsychopharmacol

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Self-administration procedures have not yet provided evidence that freely moving mice can reliably acquire and maintain an operant behavior to self-administer cannabinoid agonists. The aim of the present work was to establish a model of cannabinoid operant intravenous self-administration in freely moving mice given the relevance of this species for the use of genetically modified animals. In addition, the possible involvement of the k/dynorphin system in cannabinoid self-administration was evaluated by using pro-dynorphin knockout mice. Outbred CD1 wild-type mice as well as pro-dynorphin knockout and wild-type mice were trained to self-administer the cannabinoid receptor agonist WIN 55,212-2 under an FR1 schedule of reinforcement. Two cannabinoid training doses (6.25 and 12.5 mg/ kg/infusion) were used in the acquisition studies in outbred mice. Animals acquired a reliable operant responding to self-administer WIN 55,212-2 (12.5 mg/kg/infusion), but required as many as 15 sessions to attain this behavior. Interestingly, when a previous injection of WIN 55,212-2 (0.1 mg/kg, i.p.) was administered in the home-cage 24 h before the first session, mice acquired operant responding for cannabinoid self-administration by the fourth session. When the k-opioid agonist antagonist nor-binaltorphimine (5 mg/kg s.c.) was administered 4 h before the first session, the time required to acquire a reliable cannabinoid self-administration was also significantly reduced. Finally, a shift to the left in the dose-intake curve to self-administer WIN 55,212-2 was observed in pro-dynorphin knockout mice when compared to wild-type mice. These results indicate that the activation of the k/dynorphin opioid system after WIN 55,212-2 administration could counteract cannabinoid rewarding effects.

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“…Surprisingly, THC, as well as synthetic cannabinoid agonists, like CP 55,940 (McGregor et al, 1996), WIN 55,212-2 (Chaperon et al, 1998 and HU 210 (Cheer et al, 2000), generally induce conditioned place avoidance or aversion rather than place preference in rats (Parker and Gillies, 1995;Sanudo-Pena et al, 1997;Hutcheson et al, 1998;Mallet and Beninger, 1998) and mice (Valjent and Maldonado, 2000), although THC-induced conditioned place preferences have been reported at limited dose-ranges and under restricted experimental conditions in Long Evans rats and in mice (Lepore et al, 1995;Valjent and Maldonado, 2000;Ghozland et al, 2002) and CP 55,940-induced conditioned place preferences have been reported in Wistar rats (Braida et al, 2001a).…”

Section: Subjective and Motivational Effects Of Cannabinoidsmentioning

confidence: 99%

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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Endogenous cannabinoids as an aversive or counter-rewarding system in the rat

Cited by 148 publications

References 24 publications

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

Involvement of κ/Dynorphin System in WIN 55,212-2 Self-Administration in Mice

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

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