Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats

J. Haller, I. Barna, B. Barsvari, K. Gyimesi Pelczer, S. Yasar, L. V. Panlilio, S. Goldberg

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Rationale: Since the discovery of endogenous cannabinoid signaling, the number of studies exploring its role in health and disease has increased exponentially. Fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of the endocannabinoid anandamide, has emerged as a promising target for anxiety-related disorders. FAAH inhibitors (e.g., URB597) increase brain levels of anandamide and induce anxiolytic-like effects in rodents. Recent findings, however, questioned the efficacy of URB597 as an anxiolytic. Objectives: We tested here the hypothesis that conflicting findings are due to variations in the stressfulness of experimental conditions employed in various studies. Results: We found that URB597 (0.1-0.3 mg/kg) did not produce anxiolytic effects when the aversiveness of testing procedures was minimized by handling rats daily before experimentation, by habituating them to the experimental room, or by employing low illumination during testing. In contrast, URB597 had robust anxiolytic effects when the aversiveness of the testing environment was increased by eliminating habituation to the experimental room or by employing bright lighting conditions. Unlike URB597, the benzodiazepine chlordiazepoxide (5 mg/kg) had anxiolytic effects under all testing conditions. The anxiolytic effects of URB597 were abolished by the cannabinoid CB1-receptor antagonist AM251, showing that they were mediated by CB1 receptors. Close inspection of experimental conditions employed in earlier reports suggests that conflicting findings with URB597 can be explained by different testing conditions, such as those manipulated in the present study. Conclusions: Our findings show that FAAH inhibition does not affect anxiety under mildly stressful circumstances but protects against the anxiogenic effects of aversive stimuli.

Original languageEnglish
Pages (from-to)607-616
Number of pages10
JournalPsychopharmacology
Volume204
Issue number4
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Cannabinoids
Anti-Anxiety Agents
Lighting
Cannabinoid Receptor Antagonists
Chlordiazepoxide
Cannabinoid Receptor CB1
Endocannabinoids
Inhibition (Psychology)
cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
fatty-acid amide hydrolase
Anxiety Disorders
Benzodiazepines
Rodentia
Anxiety
Health
Brain
Enzymes

Keywords

  • Anxiety
  • Aversive
  • Elevated plus-maze
  • FAAH
  • Rat
  • Stress
  • URB597

ASJC Scopus subject areas

  • Pharmacology

Cite this

Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats. / Haller, J.; Barna, I.; Barsvari, B.; Gyimesi Pelczer, K.; Yasar, S.; Panlilio, L. V.; Goldberg, S.

In: Psychopharmacology, Vol. 204, No. 4, 07.2009, p. 607-616.

Research output: Contribution to journalArticle

Haller, J. ; Barna, I. ; Barsvari, B. ; Gyimesi Pelczer, K. ; Yasar, S. ; Panlilio, L. V. ; Goldberg, S. / Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats. In: Psychopharmacology. 2009 ; Vol. 204, No. 4. pp. 607-616.
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