The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction

Lafenêtre, Pauline; Chaouloff, Francis; Marsicano, Giovanni

doi:10.1016/j.phrs.2007.09.006

Cited by 115 publications

(92 citation statements)

References 119 publications

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“…However, our observations and those of others suggest that the performances in these fear-based memory tests might be not exclusively due to the ability to process fear memory, but also to intrinsic "coping styles" (Koolhaas et al, 2010;Gozzi et al, 2010;VicensCosta et al, 2011). CB 1 receptor signaling determines the coping style to fear conditioned stimuli by acting upon GABAergic and glutamatergic neurons In line with previous reports, ubiquitous CB 1 receptor inactivation led to a predominant freezing response in classical fear conditioning and enhanced passive and active avoidance performances (Marsicano et al, 2002;Martin et al, 2002;Lafenêtre et al, 2007;Dubreucq et al, 2010). Thus, the consequences of a total CB 1 receptor deletion on the potentiation of either passive or active fear coping strategies are task-specific.…”

Section: Conditioned Fear Responding Is Influenced By Individual Varisupporting

confidence: 87%

“…The endogenous activity of CB 1 receptors is necessary for extinction of freezing in fear conditioning and of passive avoidance learning (Marsicano et al, 2002;Lafenêtre et al, 2007;Dubreucq et al, 2010), indicating that CB 1 signaling controls passive fear responses. In contrast, the deletion of the CB 1 gene facilitates active avoidance learning (Martin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors

Metna-Laurent¹,

Soria-Gómez²,

Verrier³

et al. 2012

J. Neurosci.

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To maximize their chances of survival, animals need to rapidly and efficiently respond to aversive situations. These responses can be classified as active or passive and depend on the specific nature of threats, but also on individual fear coping styles. In this study, we show that the control of excitatory and inhibitory brain neurons by type-1 cannabinoid (CB 1 ) receptors is a key determinant of fear coping strategies in mice. In classical fear conditioning, a switch between initially predominant passive fear responses (freezing) and active behaviors (escape attempts and risk assessment) develops over time. Constitutive genetic deletion of CB 1 receptors in CB 1 Ϫ/Ϫ mice disrupted this pattern by favoring passive responses. This phenotype can be ascribed to endocannabinoid control of excitatory neurons, because it was reproduced in conditional mutant mice lacking CB 1 receptors from cortical glutamatergic neurons. CB 1 receptor deletion from GABAergic brain neurons led to the opposite phenotype, characterized by the predominance of active coping. The CB 1 receptor agonist ⌬ 9 -tetrahydrocannabinol exerted a biphasic control of fear coping strategies, with lower and higher doses favoring active and passive responses, respectively. Finally, viral re-expression of CB 1 receptors in the amygdala of CB 1 Ϫ/Ϫ mice restored the normal switch between the two coping strategies. These data strongly suggest that CB 1 receptor signaling bimodally controls the spontaneous adoption of active or passive coping strategies in individuals. This primary function of the endocannabinoid system in shaping individual behavioral traits should be considered when studying the mechanisms of physiological and pathological fear.

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Section: Conditioned Fear Responding Is Influenced By Individual Varisupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors

Metna-Laurent¹,

Soria-Gómez²,

Verrier³

et al. 2012

J. Neurosci.

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“…The role of the endocannabinoid system in fear responding per se (i.e. in the absence of nociceptive tone) has been examined extensively and the weight of evidence suggests that endocannabinoid-CB 1 receptor signalling serves to facilitate and enhance the extinction of conditioned fear responding (for review see [15,48,79]), while genetic deletion or pharmacological blockade of the CB 1 receptor attenuates short-and long-term extinction of conditioned fear responding [14,18,25,39,44,48,52,59,62,70,76]. The results of the present study, however, suggest that in the presence of formalin-evoked nociceptive tone, increased endocannabinoid signalling in the vHip (as a consequence of URB597 administration) in fact serves to inhibit rather than enhance the short-term, within-trial extinction of fear responding.…”

Section: Discussionmentioning

confidence: 99%

A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

Ford

Kieran

Dolan

et al. 2011

Pain

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“…Direct evidence for a tonic role of CB 1 receptors in the control of emotionality has been gathered by means of pharmacology and genetics. Thus, the use of CB 1 receptor antagonists and of CB 1 receptor mutant mice has underlined the prominent role of CB 1 receptors on locomotor reactivity, anxiety, and fear responses to the acute exposure to aversive environments (Viveros et al, 2005;Wotjak, 2005;Lafenêtre et al, 2007;Lutz, 2009). However, the tight interactions between the endocannabinoid system (ECS) and stress circuits are not limited to the acute exposure to aversive stimuli.…”

Section: Introductionmentioning

confidence: 99%

Genetic Dissection of the Role of Cannabinoid Type-1 Receptors in the Emotional Consequences of Repeated Social Stress in Mice

Dubreucq

Matías

Cardinal

et al. 2012

Neuropsychopharmacol

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133

117

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The endocannabinoid system (ECS) tightly controls emotional responses to acute aversive stimuli. Repeated stress alters ECS activity but the role played by the ECS in the emotional consequences of repeated stress has not been investigated in detail. This study used social defeat stress, together with pharmacology and genetics to examine the role of cannabinoid type-1 (CB 1 ) receptors on repeated stressinduced emotional alterations. Seven daily social defeat sessions increased water (but not food) intake, sucrose preference, anxiety, cued fear expression, and adrenal weight in C57BL/6N mice. The first and the last social stress sessions triggered immediate brain regiondependent changes in the concentrations of the principal endocannabinoids anandamide and 2-arachidonoylglycerol. Pretreatment before each of the seven stress sessions with the CB 1 receptor antagonist rimonabant prolonged freezing responses of stressed mice during cued fear recall tests. Repeated social stress abolished the increased fear expression displayed by constitutive CB 1 receptordeficient mice. The use of mutant mice lacking CB 1 receptors from cortical glutamatergic neurons or from GABAergic neurons indicated that it is the absence of the former CB 1 receptor population that is responsible for the fear responses in socially stressed CB 1 mutant mice. In addition, stress-induced hypolocomotor reactivity was amplified by the absence of CB 1 receptors from GABAergic neurons. Mutant mice lacking CB 1 receptors from serotonergic neurons displayed a higher anxiety but decreased cued fear expression than their wild-type controls. These mutant mice failed to show social stress-elicited increased sucrose preference. This study shows that (i) release of endocannabinoids during stress exposure impedes stress-elicited amplification of cued fear behavior, (ii) social stress opposes the increased fear expression and delayed between-session extinction because of the absence of CB 1 receptors from cortical glutamatergic neurons, and (iii) CB 1 receptors on central serotonergic neurons are involved in the sweet consumption response to repeated stress.

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The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction

Cited by 115 publications

References 119 publications

Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors

Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors

A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

Genetic Dissection of the Role of Cannabinoid Type-1 Receptors in the Emotional Consequences of Repeated Social Stress in Mice

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The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction

Cited by 115 publications

References 119 publications

Bimodal Control of Fear-Coping Strategies by CB1Cannabinoid Receptors

Bimodal Control of Fear-Coping Strategies by CB1Cannabinoid Receptors

A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

Genetic Dissection of the Role of Cannabinoid Type-1 Receptors in the Emotional Consequences of Repeated Social Stress in Mice

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Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors

Bimodal Control of Fear-Coping Strategies by CB₁Cannabinoid Receptors