Faculty Collaboration Database

Synergistic interactions between cannabinoids and environmental stress in the activation of the central amygdala. Neuropsychopharmacology 2005 Mar;30(3):497-507

Date

07/29/2004

Pubmed ID

15280883

DOI

10.1038/sj.npp.1300535

Scopus ID

2-s2.0-13944278876 (requires institutional sign-in at Scopus site)   140 Citations

Abstract

Anxiety and panic are the most common adverse effects of cannabis intoxication; reactions potentiated by stress. Data suggest that cannabinoid (CB1) receptor modulation of amygdalar activity contributes to these phenomena. Using Fos as a marker, we tested the hypothesis that environmental stress and CB1 cannabinoid receptor activity interact in the regulation of amygdalar activation in male mice. Both 30 min of restraint and CB1 receptor agonist treatment (Delta9-tetrahydrocannabinol (2.5 mg/kg) or CP55940 (0.3 mg/kg); by i.p. injection) produced barely detectable increases in Fos expression within the central amygdala (CeA). However, the combination of restraint and CB1 agonist administration produced robust Fos induction within the CeA, indicating a synergistic interaction between environmental stress and CB1 receptor activation. An inhibitor of endocannabinoid transport, AM404 (10 mg/kg), produced an additive interaction with restraint within the CeA. In contrast, fatty acid amide hydrolase (FAAH) inhibitor-treated mice (URB597, 1 mg/kg) and FAAH-/- mice did not exhibit any differences in amygdalar activation in response to restraint compared to control mice. In the basolateral (BLA) and medial amygdala, restraint stress produced a low level of Fos induction, which was unaffected by cannabinoid treatment. Interestingly, the CB1 receptor antagonist SR141716 dose-dependently increased Fos expression in the BLA and CeA. These data suggest the CeA is an important neural substrate subserving the interactions between cannabinoids and environmental stress, and could be relevant to understanding the context-dependent emotional and affective changes induced by marijuana intoxication and the role of endocannabinoid signaling in the modulation of amygdalar activity.

Author List

Patel S, Cravatt BF, Hillard CJ

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amygdala
Analgesics
Animals
Cannabinoids
Cyclohexanols
Disease Models, Animal
Dronabinol
Genes, fos
Male
Mice
Mice, Inbred ICR
Restraint, Physical
Stress, Psychological