Potential anxiogenic effects of cannabinoid CB1 receptor antagonists/inverse agonists in rats: Comparisons between AM4113, AM251, and the benzodiazepine inverse agonist FG-7142

Sink, Kelly S.; Segovia, Kristen N.; Sink, Jacquelyn R.; Randall, Patrick A.; Collins, Lyndsey E.; Correa, Mercè; Markus, Etan J.; Vemuri, V. Kiran; Makriyannis, Alexandros; Salamone, John D.

doi:10.1016/j.euroneuro.2009.11.002

Cited by 73 publications

(63 citation statements)

References 73 publications

(111 reference statements)

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“…Since FAAH inhibition failed to interfere with the CPA, the potential of the CB 1 inverse agonist/antagonist AM251 to interfere with a single-cycle morphine withdrawal CPA was evaluated. Since CB 1 inverse agonists/antagonists (SR141716 and AM251) have been shown to have adverse clinical side effects of nausea, anxiety, and depression (Bergman et al 2008; Christensen et al 2007; Sink et al 2010), the neutral CB 1 receptor antagonist, AM4113, was also assessed for its potential to interfere with the establishment of a CPA produced by naloxone-precipitated MWD. Finding both AM251 and AM4113 were successful in preventing establishment of the CPA, their potential to interfere with the reinstatement of an extinguished CPA by a naloxone-precipitated morphine prime was investigated, but such an effect was not revealed.…”

Section: Introductionmentioning

confidence: 99%

CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

et al. 2014

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Rationale Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal.

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Section: Introductionmentioning

confidence: 99%

CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

et al. 2014

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“…A dose of 5 mg/kg AM-251 was chosen based on previous literature reporting that acute exposure at this dose produces some behavioral indices of stress exposure in adult rodents such as increased anxiety-like behaviour (Litvin et al, 2013;Naderi et al, 2008;Sink et al, 2010). Thus, in the current study a moderate dose of 5 mg/kg AM-251 was used and intraperitoneally (IP) injected (or an equivalent volume of vehicle) in male rats from PND 35-45, the same cannabinoid administration period used by several studies conducted by the Parolaro laboratory (Rubino et al, 2015;Rubino et al, 2009a;Rubino et al, 2009b;Zamberletti et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

Disruption of peri-adolescent endocannabinoid signaling modulates adult neuroendocrine and behavioral responses to stress in male rats

et al. 2015

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“…In addition, AM251 reduced urocortin1 microinjection-and nicotine abstinence-induced anxieties [69,70]. Other antagonists (AM281, AM4113, and AVE1625) did not affect anxiety [66,[71][72][73].…”

Section: Decreased 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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Potential anxiogenic effects of cannabinoid CB1 receptor antagonists/inverse agonists in rats: Comparisons between AM4113, AM251, and the benzodiazepine inverse agonist FG-7142

Cited by 73 publications

References 73 publications

CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

Disruption of peri-adolescent endocannabinoid signaling modulates adult neuroendocrine and behavioral responses to stress in male rats

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

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