J 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

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

ED1.1.00/02.0068, projekt VaV
Název: CEITEC - central european institute of technology