Faculty Collaboration Database

Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur J Neurosci 2005 Feb;21(4):1057-69

Date

03/25/2005

Pubmed ID

15787710

DOI

10.1111/j.1460-9568.2005.03916.x

Scopus ID

2-s2.0-16244398653 (requires institutional sign-in at Scopus site)   256 Citations

Abstract

The role of endocannabinoid (eCB) signalling in restraint stress-induced neuronal activation was studied. Male mice exposed to 30 min of restraint exhibit increased Fos protein within prefrontal cortex (PFC), lateral septum (LS), nucleus accumbens (Acb) and medial amygdala. SR141716 (2 mg/kg) itself had no effect on Fos but pretreatment with SR141716 significantly potentiated restraint-induced Fos expression in cingulate, LS and Acb. SR141716 also significantly increased the time spent in active escape behaviours during the restraint. In restraint-habituated mice (mice exposed to four previous restraint episodes), the fifth restraint exposure resulted in decreased expression of active escape behaviours compared to the first exposure and only induced Fos protein in the central and medial amygdala. Administration of SR141716 prior to the fifth restraint episode resulted in greater potentiation of restraint-induced Fos induction than the first; significant increases occurred within all regions of PFC examined, LS and Acb. Brain regional eCB content was measured immediately after restraint. N-arachidonylethanolamine content within the amygdala was significantly decreased after both restraint episodes. 2-Arachidonylglycerol content was significantly increased in both the limbic forebrain and amygdala after the fifth restraint but not the first. Restraint had no effect on cerebellar eCB content. These data suggest that eCB activation of CB(1) receptors opposes the behavioural and neuronal responses to aversive stimuli. Because repeated homotypic stress increased both limbic 2-AG and resulted in a greater effect of SR141716 on limbic Fos expression, we hypothesize that increased CB(1) receptor activity contributes to the expression of habituation to homotypic stress.

Author List

Patel S, Roelke CT, Rademacher DJ, Hillard CJ

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

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

Analysis of Variance
Animals
Behavior, Animal
Brain Chemistry
Cannabinoid Receptor Antagonists
Cannabinoid Receptor Modulators
Cell Count
Chromatography, High Pressure Liquid
Escape Reaction
Immunohistochemistry
Male
Mass Spectrometry
Mice
Mice, Inbred ICR
Neural Inhibition
Oncogene Proteins v-fos
Piperidines
Pyrazoles
Restraint, Physical
Signal Transduction
Stress, Psychological
Time Factors