An endocannabinoid signaling system modulates anxiety-like behavior in male Syrian hamsters

Abstract

Rationale-An endocannabinoid signaling system has not been identified in hamsters.Objective-We examined the existence of an endocannabinioid signaling system in Syrian hamsters using neuroanatomical, biochemical and behavioral pharmacological approaches.Method-The distribution of cannabinoid receptors was mapped and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB 1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test and models of unconditioned and conditioned social defeat.Results-A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [ 3 H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC 50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine (PEA) and N-oleoyl ethanolamine (OEA)) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1-10 mg/kg i.p.) induced CB 1 -mediated motor ataxia. Blockade of CB 1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1-0.3 mg/kg i.p.) induced CB 1 -mediated anxiolytic-like effects in elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam (2-6 mg/ kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3-3.0 mg/kg i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance.Conclusions-Endocannabinoids engage functional CB 1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB 1 receptor activation.

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

“…their effects are more specific than those of agonists, which activate cannabinoid receptors throughout the brain. Both genetic and pharmacological blockade of the anandamide metabolizing enzyme, fatty acid amide hydrolase (FAAH), led to anxiolytic effects in a number of reports [43,46,67,71,86,100,126,128,[130][131][132][133][134][135][136][137][138]. In other cases, however, no effects were seen either after genetic [139] or pharmacological blockade of FAAH activity [138][139][140].…”

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

“…Knockout or antagonism of Cnr1 increases anxiety-like behavior on a number of different paradigms across a variety of species (149, 151, 152). Increased synthesis of the endocannabinoids and subsequent activation of Cnr1 in the amygdala is thought to mediate fear extinction in mice and rats, potentially via inhibition of the anxiogenic neuropeptide cholecystokinin (CCK) and/or modulation of the GABAergic system (151, 153, 154).…”

Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease

“…These two structures are key components of learning and memory function, and are affected in AD progression [20,21]. CB1 receptors are also more classically associated with anxietylike and aggressive behaviour in animals [22,23]. Furthermore, CB2 receptor activation has been shown to reduce the in vitro production of pro-inflammatory molecules [24,25] and induce the removal of amyloid-beta (Ab) plaques from human AD tissues [26].…”