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.
- Klíčová slova
- FAAH, HPA-axis, N-Arachidonoylserotonin, Stress, TRPV1,
- MeSH
- amidohydrolasy antagonisté a inhibitory genetika metabolismus MeSH
- chování zvířat účinky léků MeSH
- endokanabinoidy metabolismus MeSH
- fyzické omezení MeSH
- glyceridy metabolismus MeSH
- kationtové kanály TRPV antagonisté a inhibitory genetika metabolismus MeSH
- kortikosteron krev MeSH
- krysa rodu Rattus MeSH
- kyseliny arachidonové metabolismus farmakologie terapeutické užití MeSH
- mozek účinky léků metabolismus MeSH
- mozkový neurotrofický faktor genetika metabolismus MeSH
- plavání MeSH
- polynenasycené alkamidy metabolismus MeSH
- potkani Wistar MeSH
- psychický stres krev farmakoterapie metabolismus MeSH
- serotonin analogy a deriváty farmakologie terapeutické užití MeSH
- systém hypofýza - nadledviny MeSH
- systém hypotalamus-hypofýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amidohydrolasy MeSH
- anandamide MeSH Prohlížeč
- arachidonoylserotonin MeSH Prohlížeč
- endokanabinoidy MeSH
- fatty-acid amide hydrolase MeSH Prohlížeč
- glyceridy MeSH
- glyceryl 2-arachidonate MeSH Prohlížeč
- kationtové kanály TRPV MeSH
- kortikosteron MeSH
- kyseliny arachidonové MeSH
- mozkový neurotrofický faktor MeSH
- polynenasycené alkamidy MeSH
- serotonin MeSH
- Trpv1 protein, rat MeSH Prohlížeč
