Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat

Navarro, Miguel; Hernández, Enrique; Muñoz, Riansares; Arco, Ignacio del; Villanúa, María Ángeles; Carrera, Marta; Fonseca, Fernando Rodrı́guez de

doi:10.1097/00001756-199701200-00023

Cited by 277 publications

(202 citation statements)

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“…In rats, for example, a single electric shock to the paw elevates anandamide levels in the midbrain (Hohmann et al, 2005), while in mice physical restraint decreases anandamide levels in the amygdala (Patel et al, 2004). Moreover, pharmacological blockade or genetic ablation of CB 1 receptors exacerbates normal reactions to acute stress, presumably by disabling an endocannabinoid modulation of these reactions (Navarro et al, 1997;Haller et al, 2004;Urigüen et al, 2004). Finally, the FAAH inhibitor URB597 enhances stress-coping behaviors in a rimonabant-sensitive manner (Kathuria et al, 2003;Gobbi et al, 2005), suggesting that anandamide interacts with a subgroup of CB 1 receptors in the brain that regulate stress responses.…”

Section: Discussionmentioning

confidence: 99%

Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404

Bortolato

Campolongo

Mangieri

et al. 2006

Neuropsychopharmacol

212

150

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The endocannabinoids anandamide and 2-arachidonoyglycerol (2-AG) may contribute to the regulation of mood and emotion. In this study, we investigated the impact of the endocannabinoid transport inhibitor AM404 on three rat models of anxiety: elevated plus maze, defensive withdrawal and separation-induced ultrasonic vocalizations. AM404 (1-5 mg kg À1 , intraperitoneal (i.p.)) exerted dosedependent anxiolytic-like effects in the three models. These behavioral effects were associated with increased levels of anandamide, but not 2-AG, in the prefrontal cortex and were prevented by the CB 1 cannabinoid antagonist rimonabant (SR141716A), suggesting that they were dependent on anandamide-mediated activation of CB 1 cannabinoid receptors. We also evaluated whether AM404 might influence motivation (in the conditioned place preference (CPP) test), sensory reactivity (acoustic startle reflex) and sensorimotor gating (prepulse inhibition (PPI) of the startle reflex). In the CPP test, AM404 (1.25-10 mg kg À1 , i.p.) elicited rewarding effects in rats housed under enriched conditions, but not in rats kept in standard cages. Moreover, AM404 did not alter reactivity to sensory stimuli or cause overt perceptual distortion, as suggested by its lack of effect on startle or PPI of startle. These results support a role of anandamide in the regulation of emotion and point to the anandamide transport system as a potential target for anxiolytic drugs.

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Section: Discussionmentioning

confidence: 99%

Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404

Bortolato

Campolongo

Mangieri

et al. 2006

Neuropsychopharmacol

212

150

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“…CCK has been shown to enhance memory formation by acting on hippocampal neurons, and have strong anxiogenic effects, whereas cannabinoids interfere with memory formation and the endogenous tone they mediate may alleviate anxiety. 17,32,37,41 One may argue that the magnitude of suppression of GABA release (ϳ50%) is much higher than the number of CCK-containing interneurons in the hippocampus estimated to represent only 10-20% of all hippocampal interneurons in the rat. Indeed, not all CB1-containing interneurons expressed CCK (see Table 1 for details).…”

Section: Cb1 Cannabinoid Receptor Activation Leads To a Reduction Of mentioning

confidence: 99%

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

et al. 2000

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Abstract-Cannabinoids have been shown to disrupt memory processes in mammals including humans. Although the CB1 neuronal cannabinoid receptor was identified several years ago, neuronal network mechanisms mediating cannabinoid effects are still controversial in animals, and even more obscure in humans. In the present study, the localization of CB1 receptors was investigated at the cellular and subcellular levels in the human hippocampus, using control post mortem and epileptic lobectomy tissue. The latter tissue was also used for [ 3 H]GABA release experiments, testing the predictions of the anatomical data. Detectable expression of CB1 was confined to interneurons, most of which were found to be cholecystokinin-containing basket cells. CB1-positive cell bodies showed immunostaining in their perinuclear cytoplasm, but not in their somadendritic plasmamembrane. CB1-immunoreactive axon terminals densely covered the entire hippocampus, forming symmetrical synapses characteristic of GABAergic boutons. Human temporal lobectomy samples were used in the release experiments, as they were similar to the controls regarding cellular and subcellular distribution of CB1 receptors. We found that the CB1 receptor agonist, WIN 55,212-2, strongly reduced [ 3 H]GABA release, and this effect was fully prevented by the specific CB1 receptor antagonist SR 141716A.This unique expression pattern and the presynaptic modulation of GABA release suggests a conserved role for CB1 receptors in controlling inhibitory networks of the hippocampus that are responsible for the generation and maintenance of fast and slow oscillatory patterns. Therefore, a likely mechanism by which cannabinoids may impair memory and associational processes is an alteration of the fine-tuning of synchronized, rhythmic population events. ᭧ 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: CB1 receptor, cholecystokinin, presynaptic, synchronization, memory, release.Most behavioral effects of the active compound of marijuana and hashish are mediated by the CB1 cannabinoid receptor (CB1). 23 Although the impacts of cannabinoid-consumption on human and animal behaviour are well known, 1,3,7,43 the underlying physiological processes and the precise sites of cannabinoid actions in neural networks remain to be identified. The hippocampal formation is one of the brain areas with the highest level of CB1 receptor expression. 18,26,29 In accordance, at the behavioral level, cannabinoids typically interfere with hippocampal functions, i.e. they disrupt memory consolidation and associations both in humans and animals. 3,17 Although several recent experiments attempted to determine the mechanisms of cannabinoid action and the precise cellular and subcellular localization of the CB1 receptor in the rodent and primate hippocampus, the data they provide are inconsistent. 4,20,27,31,34,35,38,44,45 In the rodent hippocampus, a specific class of GABAergic interneurons was shown to express CB1 receptors. 20,27,45 Detailed electron microscopic investigation rev...

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“…Indeed, it has been clearly demonstrated that cannabinoid signaling is involved in the control of anxiety, albeit it has been difficult to define the exact role of this signaling. In particular, both anxiolytic-and anxiogenic-like effects have been reported by using cannabinoid receptor agonists at low and high doses, respectively [14], and also by CB1 receptor antagonists [15,16]. These opposite observations might be explained by the distribution of CB1 receptors in the brain.…”

Section: Discussionmentioning

confidence: 99%

Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

Cannizzaro

Malta

Argo

et al. 2016

Forensic Science International

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The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018.In present study, the effects of APICA (1-3 mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3 mg/kg, i.p.) or the CB2 antagonist AM630 (3 mg/kg, i.p.) was carried out to characterize APICA activity.Our results show that APICA was able to dose-dependently decrease locomotor activity and behavioural reactivity in the open field, whereas only the highest dose was able to induce hypothermia, analgesia, motor incoordination and recognition memory impairment, with respect to vehicle (p < 0.01; p < 0.001).The pretreatment with the CB1 antagonist AM251 elicited an increase in body temperature, total distance travelled in the open field, latency to fall down in the Rotarod, and a decrease in tail flick latency (p < 0.05; p < 0.01). On the other hand, pretreatment with AM630 did not induced significant differences on APICA effects.This study supports preliminary reports on APICA cannabinomimetic properties, extending its detrimental effects on cognitive function. Moreover, these properties can be attributed to the CB1 receptor activity, indicating APICA as a selective CB1 receptor agonist

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Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat

Cited by 277 publications

References 1 publication

Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404

Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

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