title: Swim stress differentially affects limbic contents of 2-arachidonoylglycerol and 2-oleoylglycerol.
abstract: Restraint stress exposures evoke progressively larger increases in 2-arachidonoylglycerol (2-AG) in limbic brain regions as the number of repetitions increases. The Porsolt swim test usually involves two swim exposures separated by 24 h, and we asked whether the 2-AG response differed between the first and second exposures.
  
  
  METHODS
  Four groups of male C57/Bl6N mice were studied: control; exposed to a single 6 min swim and killed immediately; exposed to a single 6 min swim and killed 24 h later; and exposed to two swims, separated by 24 h, and killed after the second swim. Outcomes were swim behavior, serum corticosterone, and 2-AG and 2-oleoylglycerol (2-OG) contents in amygdala, hippocampus, and prefrontal cortex.
  
  
  RESULTS
  Mean 2-AG contents were not significantly different among the four treatment groups in any brain region and did not correlate with immobility in either forced swim exposure. However, 2-AG contents in all three brain regions only of the mice exposed to two swims were significantly, positively correlated with serum corticosterone concentrations measured at the same time. 2-OG is present in brain and exhibits a striking regional heterogeneity in control mice. 2-OG concentrations in prefrontal cortex were significantly reduced in the mice killed on the second day compared with the mice killed on the first day. As the target of 2-OG in brain is not known, the significance of these observations await further studies.
  
  
  CONCLUSIONS
  Although prior exposure to swim stress does not alter brain 2-AG contents upon re-exposure, 2-AG concentrations in brain become significantly correlated with the hypothalamic-pituitary-adrenal (HPA) axis response to stress when prior exposure to the stress has occurred. These data suggest that even a single exposure to a short period of intense stress sensitizes the 2-AG response to re-exposure to that situation and are consistent with a role for endocannabinoid signaling in modulating stress responses.
authors.affiliation: Department of Pharmacology and Toxicology and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: K L
authors.initials: KL
authors.lastname: Stuhr
authors.forename: C J
authors.initials: CJ
authors.lastname: Hillard
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*; D013550:Swimming
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate; C505247:2-oleoylglycerol; D003345:Corticosterone