2015
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons
LLORENTE-BERZAL, Alvaro; Ana Luisa B. TERZIAN; Vincenzo DI MARZO; Vincenzo MICALE; Maria Paz VIVEROS et al.Základní údaje
Originální název
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons
Autoři
LLORENTE-BERZAL, Alvaro; Ana Luisa B. TERZIAN; Vincenzo DI MARZO; Vincenzo MICALE; Maria Paz VIVEROS a Carsten T. WOTJAK
Vydání
Psychopharmacology, New York, Springer, 2015, 0033-3158
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30000 3. Medical and Health Sciences
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 3.540
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14740/15:00084725
Organizační jednotka
Středoevropský technologický institut
UT WoS
EID Scopus
Klíčová slova anglicky
Fear extinction; TRPV1; CB1; CB2; URB597; JZL184; AM404; Anandamide
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 1. 4. 2016 15:59, Mgr. Eva Špillingová
Anotace
V originále
The contribution of two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), in the regulation of fear expression is still unknown. We analyzed the role of different players of the endocannabinoid system on the expression of a strong auditory-cued fear memory in male mice by pharmacological means. The cannabinoid receptor type 1 (CB1) antagonist SR141716 (3 mg/kg) caused an increase in conditioned freezing upon repeated tone presentation on three consecutive days. The cannabinoid receptor type 2 (CB2) antagonist AM630 (3 mg/kg), in contrast, had opposite effects during the first tone presentation, with no effects of the transient receptor potential vanilloid receptor type 1 (TRPV1) antagonist SB366791 (1 and 3 mg/kg). Administration of the CB2 agonist JWH133 (3 mg/kg) failed to affect the acute freezing response, whereas the CB1 agonist CP55,940 (50 mu g/kg) augmented it. The endocannabinoid uptake inhibitor AM404 (3 mg/kg), but not VDM11 (3 mg/kg), reduced the acute freezing response. Its co-administration with SR141716 or SB366791 confirmed an involvement of CB1 and TRPV1. AEA degradation inhibition by URB597 (1 mg/kg) decreased, while 2-AG degradation inhibition by JZL184 (4 and 8 mg/kg) increased freezing response. As revealed in conditional CB1-deficient mutants, CB1 on cortical glutamatergic neurons alleviates whereas CB1 on GABAergic neurons slightly enhances fear expression. Moreover, 2-AG fear-promoting effects depended on CB1 signaling in GABAergic neurons, while an involvement of glutamatergic neurons remained inconclusive due to the high freezing shown by vehicle-treated Glu-CB1-KO. Our findings suggest that increased AEA levels mediate acute fear relief, whereas increased 2-AG levels promote the expression of conditioned fear primarily via CB1 on GABAergic neurons.
Návaznosti
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