title: Inhibition of anandamide hydrolysis enhances noradrenergic and GABAergic transmission in the prefrontal cortex and basolateral amygdala of rats subjected to acute swim stress.
abstract: Limbic forebrain endocannabinoid (eCB) signaling is critically involved in stress integration by modulating neurotransmitters release. The purpose of this study was to examine, by brain microdialysis, the effects of fatty acid amide hydrolase (FAAH) inhibition on noradrenergic and γ-aminobutyric acid (GABA)-ergic neurotransmission in the prefrontal cortex (PFC) and basolateral amygdala (BLA) of rats subjected to a 20-min swim stress. Microdialysis started on stress- and drug-naïve rats that were treated with the FAAH inhibitor URB597 (0.1 or 0.3 mg/kg) 30 min before undergoing the stress procedure. Dialysate samples were collected every 20 min from the beginning of the experiment. Concentrations of noradrenaline (NA) and GABA were determined by HPLC coupled to electrochemical and fluorescence detection, respectively. We found that neither URB597 treatment nor 20 min of swim stress exposure per se altered NA and GABA extracellular levels in PFC or BLA. Interestingly, rats treated with 0.1 mg/kg of URB597 followed by 20 min of stress showed significantly higher NA and GABA levels in PFC and BLA. These effects were absent in rats treated with 0.3 mg/kg URB597, indicating a dose-specific effect. Moreover, we found that the pretreatment with the CB1 receptor antagonist rimonabant blocked the URB597 effects on NA and GABA release in PFC and BLA of animals subjected to forced swimming. The present study might provide an important first step toward understanding the mechanisms through which URB597 modulates stress-induced neuroendocrine secretion and behavioral coping strategies.
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bedse
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.forename: Bianca
authors.initials: B
authors.lastname: Tempesta
authors.forename: Michele A
authors.initials: MA
authors.lastname: Lavecchia
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pace
authors.forename: Antonello
authors.initials: A
authors.lastname: Bellomo
authors.forename: Andrea
authors.initials: A
authors.lastname: Duranti
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Micioni Di Bonaventura
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D017397:Prefrontal Cortex; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000473:pathology*; D013550:Swimming / Q000523:psychology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D001549:Benzamides; D002219:Carbamates; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D005680:gamma-Aminobutyric Acid; C078814:anandamide; D009638:Norepinephrine
keywords: GABA; URB597; anandamide; basolateral amygdala; noradrenaline; prefrontal cortex