Unconditioned and conditioned anxiogenic effects of the cannabinoid receptor agonist CP 55,940 in the social interaction test

Genn, Rachel F.; Tucci, Sonia; Marco, Eva M.; Viveros, María-Paz; File, Sandra E.

doi:10.1016/j.pbb.2003.12.019

Cited by 81 publications

(52 citation statements)

References 39 publications

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“…The observed anxiogenic effects of cannabinoids agree with previous results in the emergence and EPM tests (Rodriguez de Fonseca et al, 1996;Arevalo et al, 2001;Caberlotto et al, 2004;Marco et al, 2004) and the social interaction test (Genn et al, 2004). Adolescent behavior in rodents is characterized by greater social interaction and exploratory behavior relative to adults (Spear, 2000) and such effects were evident in control rats in the social interaction and EPM tasks in the present study.…”

Section: Acute Anxiogenic Effects Of Thcsupporting

confidence: 93%

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 Anxiogenic Effects Of Thcsupporting

confidence: 93%

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 observation that THC reduced reactivity to threat-related stimuli is consistent with other evidence that cannabinoids play a role in fear and anxiety. Although high doses of THC may appear to increase anxiety (D'Souza et al, 2004;Genn et al, 2004;Viveros et al, 2005), low doses of cannabinoid receptor (CB 1 ) agonists, including THC, attenuate anxiety responses in animal models of fear and anxiety, including the elevated plus-maze and social interaction tests (Onaivi et al, 1990;Navarro et al, 1993;Rodriguez de Fonseca et al, 1997;Berrendero and Maldonado, 2002). In contrast, genetic disruption of the CB 1 receptor and selective pharmacological CB 1 antagonism enhance anxiety responses (Rodriguez de Fonseca et al, 1997;Hajos and Freund, 2002;Haller et al, 2002;Martin et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans

Phan¹,

Angstadt²,

Golden³

et al. 2008

J. Neurosci.

225

186

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The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of ⌬ 9 -tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB 1 receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid system for disorders of anxiety and social fear.

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“…In the elevated plus maze, cannabinoid agonists generally produce anxiogenic effects at high doses and anxiolytic effects at low doses (Arevalo et al, 2001;Berrendero and Maldonado, 2002;Marin et al, 2003;Marco et al, 2004). In the social interaction test (File, 1992;File and Seth, 2003;Genn et al, 2004) and defensive withdrawal test (Rodriguez de Fonseca et al, 1996;Yang et al, 1992), cannabinoid agonists and psychomotor stimulants can both produce anxiogenic effects. Acute administration of cocaine has been found to be anxiogenic in the light/dark test (Costall et al, 1989b), elevated plus maze (DeVries and Pert, 1998;Paine et al, 2002;Rogerio and Takahashi, 1992;Yang et al, 1992), drinking conflict test (Fontana and Commissaris, 1989), pentylenetetrazol drug discrimination (Shearman and Lal, 1981), and runway self-administration procedures (Ettenberg, 2004).…”

Section: Discussionmentioning

confidence: 99%

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol (THC) exposure, then allowing them to self-administer other drugs. In Experiment 1, THC preexposure did not alter the acquisition of cocaine self-administration or the amount of cocaine taken under a fixed-ratio 1 (FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine-seeking was significantly reduced in THC-exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive-ratio schedule, but it increased heroin self-administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC-exposed rats under FR1 heroin self-administration. When given cocaine, THCexposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC preexposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effectFwhich was verified in Experiment 3 using another model of anxiety, the light-dark testFmay explain the reduced reinforcing value of cocaine observed in THC-exposed rats in Experiment 1.

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Unconditioned and conditioned anxiogenic effects of the cannabinoid receptor agonist CP 55,940 in the social interaction test

Cited by 81 publications

References 39 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

Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

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