The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24861565
DOI
10.1016/j.phrs.2014.04.014
PII: S1043-6618(14)00067-X
Knihovny.cz E-resources
- Keywords
- FAAH, HPA-axis, N-Arachidonoylserotonin, Stress, TRPV1,
- MeSH
- Amidohydrolases antagonists & inhibitors genetics metabolism MeSH
- Behavior, Animal drug effects MeSH
- Endocannabinoids metabolism MeSH
- Restraint, Physical MeSH
- Glycerides metabolism MeSH
- TRPV Cation Channels antagonists & inhibitors genetics metabolism MeSH
- Corticosterone blood MeSH
- Rats MeSH
- Arachidonic Acids metabolism pharmacology therapeutic use MeSH
- Brain drug effects metabolism MeSH
- Brain-Derived Neurotrophic Factor genetics metabolism MeSH
- Swimming MeSH
- Polyunsaturated Alkamides metabolism MeSH
- Rats, Wistar MeSH
- Stress, Psychological blood drug therapy metabolism MeSH
- Serotonin analogs & derivatives pharmacology therapeutic use MeSH
- Pituitary-Adrenal System MeSH
- Hypothalamo-Hypophyseal System MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amidohydrolases MeSH
- anandamide MeSH Browser
- arachidonoylserotonin MeSH Browser
- Endocannabinoids MeSH
- fatty-acid amide hydrolase MeSH Browser
- Glycerides MeSH
- glyceryl 2-arachidonate MeSH Browser
- TRPV Cation Channels MeSH
- Corticosterone MeSH
- Arachidonic Acids MeSH
- Brain-Derived Neurotrophic Factor MeSH
- Polyunsaturated Alkamides MeSH
- Serotonin MeSH
- Trpv1 protein, rat MeSH Browser
In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.
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