Effects of acute and repeated restraint stress on endocannabinoid content in the amygdala, ventral striatum, and medial prefrontal cortex in mice.
Endocannabinoid signaling has been implicated in habituation to repeated stress. The hypothesis that repeated exposures to stress alters endocannabinoid signaling in the limbic circuit was tested by restraining male mice for 30 min/day for 1, 7, or 10 days and measuring brain endocannabinoid content. Amygdalar N-arachidonylethanolamine was decreased after 1, 7, and 10 restraint episodes; 2-arachidonylglycerol was increased after the 10th restraint. A similar pattern occurred in the medial prefrontal cortex (mPFC): N-arachidonylethanolamine was decreased after the 7th and 10th restraints and 2-arachidonylglycerol was increased after the 10th restraint. In the ventral striatum, the pattern reversed: N-arachidonylethanolamine was increased after the 10th restraint and 2-arachidonylglycerol was decreased after the 7th restraint. Palmitoylethanolamide contents changed in parallel with N-arachidonylethanolamine in the amygdala and ventral striatum. A single restraint episode did not affect the activity of fatty acid amide hydrolase (FAAH) in any of the brain regions examined. After the 10th restraint, both V(max) and K(m) for N-arachidonylethanolamine were increased in the mPFC; while only the V(max) was increased in the amygdala. On the other hand, the V(max) of FAAH was decreased in ventral striatum after the 10th restraint. After the 10th restraint, the maximum velocity for 2-oleoylglycerol hydrolysis was increased in mPFC; no other changes in 2-oleoylglycerol hydrolysis occurred. Repeated exposure to restraint produced no changes in CB(1) receptor density in any of the areas examined. These studies are consistent with the hypothesis that stress exposure alters endocannabinoid signaling in the brain and that alterations in endocannabinoid signaling occur during habituation to stress.
Rademacher
David J
DJ
Medical College of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Meier
Sarah E
SE
Shi
Leyu
L
Ho
W-S Vanessa
WS
Jarrahian
Abbas
A
Hillard
Cecilia J
CJ
D000581:Amidohydrolases / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003511:Cyclohexanols / Q000493:pharmacokinetics; D063388:Endocannabinoids; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005989:Glycerides / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017397:Prefrontal Cortex / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D003345:Corticosterone; D003511:Cyclohexanols; D063388:Endocannabinoids; D005989:Glycerides; D014316:Tritium; D000099252:Fatty Acid Amide Hydrolases; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C505247:2-oleoylglycerol