Cannabinoid receptors and reward in the rat: a conditioned place preference study

Cheer, Joseph F.; Kendall, David A.; Marsden, C.A.

doi:10.1007/s002130000481

Cited by 141 publications

(114 citation statements)

References 33 publications

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“…This work confirms previous findings that cannabinoid agonists are aversive to rats, as shown by the formation of a conditioned place aversion (McGregor et al, 1996;SanudoPena et al, 1997;Mallet and Beninger, 1998;Cheer et al, 2000). D 9 -THC-treated adult rats avoided the drug-paired side after both four and eight contextual pairings, while adolescent rats only showed a trend toward place aversion, and only after eight pairings.…”

Section: Acute Aversive Effects Of Thcsupporting

confidence: 91%

“…This hypothesis has not to our knowledge been tested using animal models. Rats generally find cannabinoids aversive, with D-9-tetrahydrocannabinol (D 9 -THC) and synthetic cannabinoids producing conditioned place aversion (Parker and Gillies, 1995;McGregor et al, 1996;Sanudo-Pena et al, 1997;Mallet and Beninger, 1998;Cheer et al, 2000) and conditioned taste avoidance (Parker and Gillies, 1995;McGregor et al, 1996). Reports of dysphoria and panic by human cannabis users (Hall et al, 1994) suggest these aversive effects may sometimes have a human correlate.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Quinn

Matsumoto

Callaghan

et al. 2007

Neuropsychopharmacol

274

226

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The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to D-9-tetrahydrocannabinol (D 9 -THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28 + ) or adult (post-natal day 60 + ) developmental stages. Adult rats avoided a D 9 -THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final D 9 -THC injection. In contrast, adolescent rats showed no significant place aversion. Adult D 9 -THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent D 9 -THC pretreated rats showed decreased social interaction, while only D 9 -THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last D 9 -THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual D 9 -THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent D 9 -THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in D 9 -THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated D 9 -THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.

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Section: Acute Aversive Effects Of Thcsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Quinn

Matsumoto

Callaghan

et al. 2007

Neuropsychopharmacol

274

226

View full text Add to dashboard Cite

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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: 77%

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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“…Previous reports have found that lower doses of THC are not effective as conditioning stimuli in place conditioning procedures (Mallet and Beninger, 1998;Parker and Gillies, 1995;Robinson et al, 2003). In contrast, higher doses of cannabinoids such as CP 55,940 (McGregor et al, 1996), WIN 55212-2 (Chaperon et al, 1998), THC (Sanudo-Pena et al, 1997); (Cheer et al, 2000); (Hutcheson et al, 1998); (Parker and Gillies, 1995), and HU210 (Cheer et al, 2000) produced aversion in place conditioning procedures in both rats and mice. Further, the aversive effects produced by THC were blocked by the cannabinoid receptor antagonist, SR141716A (Chaperon et al, 1998), suggesting that these effects were CB1 receptor-mediated.…”

Section: Place Conditioning Effects Of Thc and Cbdmentioning

confidence: 92%

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

Vann

Gamage

Warner

et al. 2008

Drug and Alcohol Dependence

114

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Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Δ 9 -tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids [e.g., cannabidiol (CBD)] has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC's abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/ A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10 mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC's discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios.

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Cannabinoid receptors and reward in the rat: a conditioned place preference study

Abstract: The aversive effects of cannabinoid agonists and the rewarding effect of the cannabinoid antagonist are suggestive of a cannabinergic tone in the rat brain. Further research is needed to determine the precise relationship of that tone with the reward pathways of the brain.

Cited by 141 publications

References 33 publications

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

Adolescent Rats Find Repeated Δ9-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure

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

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

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