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Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.
- Source :
-
Neurotoxicity research [Neurotox Res] 2014 Aug; Vol. 26 (2), pp. 190-206. Date of Electronic Publication: 2014 Mar 21. - Publication Year :
- 2014
-
Abstract
- The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery.
- Subjects :
- Acetylcysteine pharmacology
Amides
Amidohydrolases antagonists & inhibitors
Amidohydrolases metabolism
Animals
Benzamides pharmacology
Brain metabolism
Carbamates pharmacology
Citalopram pharmacology
Enzyme Inhibitors pharmacology
Expectorants pharmacology
Imipramine pharmacology
Male
Rats, Wistar
Thiazepines pharmacology
Antidepressive Agents pharmacology
Arachidonic Acids metabolism
Brain drug effects
Endocannabinoids metabolism
Ethanolamines metabolism
Glycerides metabolism
Oleic Acids metabolism
Palmitic Acids metabolism
Polyunsaturated Alkamides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-3524
- Volume :
- 26
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurotoxicity research
- Publication Type :
- Academic Journal
- Accession number :
- 24652522
- Full Text :
- https://doi.org/10.1007/s12640-014-9465-0