Cannabinoid type 1 receptor ligands WIN 55,212-2 and AM 251 alter anxiety-like behaviors of marmoset monkeys in an open-field test

Cagni, Priscila; Barros, Marília

doi:10.1016/j.bbr.2012.11.018

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…This finding is in accordance with previous studies reporting anxiolytic effects for CB1 receptors. For example, Cagni et al [18] recently reported that WIN55212,2 has anxiolytic effects in marmoset monkeys in open field test. Intra-amygdala injection of ACPA, a CB1 receptor agonist, decreased anxiety-like behaviors in rats [19].…”

Section: Discussionmentioning

confidence: 99%

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

Rahimi

Moghaddam

Roohbakhsh

2015

Fundamemntal Clinical Pharma

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G-protein-coupled receptor 55 (GPR55) has been proposed as an atypical cannabinoid receptor, which is activated by lysophosphatidylinositols and some synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors in the central nervous system especially in anxiety needs to be evaluated. In this study, the effects of intracerebroventricular (i.c.v.) administration of agonist and antagonist of GPR55 receptor on anxiety-related behaviors in rats were investigated. Here, O-1602 (GPR55 agonist) at the doses of 0.2, 1, and 5 μg/rat increased %OAT and %OAE but not the locomotor activity, showing an anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the doses of 0.1 and 1 μg/rat increased anxiety-like behaviors while causing locomotor impairment. The antagonistic effect of ML193 on the anxiolytic-like effect of O-1602 was also evaluated. The results showed that ML193 decreased the anxiolytic-like effect of O-1602. Based on these results, it may be concluded that central GPR55 may have a role in modulation of anxiety-like behaviors in rats. Further experiments are needed to elucidate the exact role of these receptors in anxiety.

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Section: Discussionmentioning

confidence: 99%

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

Rahimi

Moghaddam

Roohbakhsh

2015

Fundamemntal Clinical Pharma

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“…The aversive and anxiogenic effects of cannabinoid receptor agonists are well described in adult rats (Cagni and Barros 2013; Quinn et al 2008; Schramm-Sapyta et al 2007). However, there is greater heterogeneity reported for behavioral responses in adolescent subjects following cannabinoid administration.…”

Section: Discussionmentioning

confidence: 99%

Repeated administration of a synthetic cannabinoid receptor agonist differentially affects cortical and accumbal neuronal morphology in adolescent and adult rats

et al. 2014

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Recent studies demonstrate a differential trajectory for cannabinoid receptor expression in cortical and sub-cortical brain areas across postnatal development. In the present study, we sought to investigate whether chronic systemic exposure to a synthetic cannabinoid receptor agonist causes morphological changes in the structure of dendrites and dendritic spines in adolescent and adult pyramidal neurons in the medial prefrontal cortex (mPFC) and medium spiny neurons (MSN) in the nucleus accumbens (Acb). Following systemic administration of WIN 55,212-2 in adolescent (PN 37–40) and adult (P55–60) male rats, the neuronal architecture of pyramidal neurons and MSN was assessed using Golgi–Cox staining. While no structural changes were observed in WIN 55,212-2-treated adolescent subjects compared to control, exposure to WIN 55,212-2 significantly increased dendritic length, spine density and the number of dendritic branches in pyramidal neurons in the mPFC of adult subjects when compared to control and adolescent subjects. In the Acb, WIN 55,212-2 exposure significantly decreased dendritic length and number of branches in adult rat subjects while no changes were observed in the adolescent groups. In contrast, spine density was significantly decreased in both the adult and adolescent groups in the Acb. To determine whether regional developmental morphological changes translated into behavioral differences, WIN 55,212-2-induced aversion was evaluated in both groups using a conditioned place preference paradigm. In adult rats, WIN 55,212-2 administration readily induced conditioned place aversion as previously described. In contrast, adolescent rats did not exhibit aversion following WIN 55,212-2 exposure in the behavioral paradigm. The present results show that synthetic cannabinoid administration differentially impacts cortical and sub-cortical neuronal morphology in adult compared to adolescent subjects. Such differences may underlie the disparate development effects of cannabinoids on behavior.

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“…For instance, the CB 1 R blocker AM251 did not show the biphasic effect seen with rimonabant. This antagonist proved to be anxiogenic over a wide range of doses (0.3-8 mg/kg) [21,25,50,[64][65][66][67][68]. In addition, AM251 reduced urocortin1 microinjection-and nicotine abstinence-induced anxieties [69,70].…”

Section: Decreased Endocannabinoid Activitymentioning

confidence: 98%

“…Surprisingly, however, the effects are not only biphasic but entirely similar to those seen with rimonabant (but not other antagonists): low doses decrease, while high doses increase anxiety. Anxiolytic effects were shown for low doses of the phytocannabinoid Δ 9 -tetrahydrocannabinol (THC; 0.075-2 mg/kg), the endocannabinoid anandamide (AEA; 0.1-1.25 mg/kg) and synthetic cannabinoids (WIN55,212-2: 0.5-3 mg/kg; CP55,940: < 0.1 mg/kg; HU210: 0.01 mg/kg) [21,43,53,65,67,68,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. Higher doses of the same agonists (THC: 2.5-10 mg/ kg; AEA: 10 mg/kg; WIN55,212-2: 3-5 mg/kg; CP55,940: > 0.1 mg/kg; HU210: 0.05-0.1 mg/kg) were anxiogenic [40,44,71,78,83,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104].…”

Section: Increased Endocannabinoid Activitymentioning

confidence: 99%

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Aliczki

Haller

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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Cannabinoid signaling is believed to decrease anxiety, albeit the conflicting nature of evidence is generally acknowledged. Here we provide a comprehensive overview of available findings by grouping them according to the tools that have been used to modulate cannabinoid signaling. The systemic administration of cannabinoid receptor agonists and antagonists led to the most conflicting findings; such treatments may increase, decrease, or leave anxiety unaffected. In addition, antagonists and agonists had similar effects in many instances including their biphasic effects. The effects of genetic manipulations, cannabinoid synthesis or reuptake inhibition as well as the effects of local brain treatments with cannabinoid ligands appear more consistent. We suggest that systemically administered receptor ligands affect cannabinoid signaling globally and as such lack the spatial and temporal specificity of endocannabinoid signaling. By contrast, gene disruption and the indirect modulation of endocannabinoid availability affect ongoing (natural) processes and lead to more specific and consistent effects. Local brain treatments whit receptor ligands are spatially restricted which increases the consistency of findings, but also reveals that cannabinoids affect anxiety in a brain area-specific manner, which further explains the inconsistency of findings with systemically injected ligands. Environmental conditions have a large impact on effects with all techniques, suggesting that endocannabinoid signaling affects coping with environmental challenges rather than unconditionally decreasing anxiety. The relationship between cannabinoid signaling, anxiety and coping styles is largely understudied, but holds great promise for understanding the roles of cannabinoids in behavioral control and may broaden their therapeutic implications.

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Cannabinoid type 1 receptor ligands WIN 55,212-2 and AM 251 alter anxiety-like behaviors of marmoset monkeys in an open-field test

Cited by 11 publications

References 22 publications

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

Repeated administration of a synthetic cannabinoid receptor agonist differentially affects cortical and accumbal neuronal morphology in adolescent and adult rats

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

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