We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
N-arachidonoyl-serotonin, a dual FAAH and TRPV1 blocker, inhibits the retrieval of contextual fear memory: Role of the cannabinoid CB1 receptor in the dorsal hippocampus.
- Authors
Gobira, Pedro H.; Lima, Isabel V.; Batista, Luara A.; de Oliveira, Antônio C.; Resstel, Leonardo B.; Wotjak, Carsten T.; Aguiar, Daniele C.; Moreira, Fabricio A.
- Abstract
Anandamide, an endocannabinoid, inhibits aversive responses by activating the CB1 cannabinoid receptor. At high concentrations, however, anandamide may exert pro-aversive activities mediated by the transient receptor potential vanilloid type-1 channel (TRPV1). Accordingly, N-arachidonoyl-serotonin (AA-5-HT), a dual blocker of the anandamide-hydrolysing enzyme fatty acid amide hydrolase (FAAH) and the TRPV1 channel, induces anxiolytic-like effects. Here we tested the hypothesis that AA-5-HT inhibits the expression of contextual fear conditioning by facilitating CB1 receptor signalling in the dorsal hippocampus of mice. Intraperitoneal injection of AA-5-HT (0.1, 0.3, 1 mg/kg) inhibited the retrieval of contextual fear memory (freezing response). The effect of AA-5-HT (0.3 mg/kg) was prevented by systemic injection of the CB1 receptor antagonist, AM251 (1.0 mg/kg), and mimicked by simultaneous FAAH inhibition (URB597, 0.3 mg/kg) and TRPV1 blockage (SB366791, 1 mg/kg). Injection of AA-5-HT (0.125, 0.25, 0.5 nmol) into the dorsal hippocampus also reduced freezing. Finally, the effect of systemic AA-5-HT (0.3 mg/kg) was prevented by intra-hippocampal injection of AM251 (1 nmol). In conclusion, dual FAAH and TRPV1 blockage inhibits contextual fear memory by facilitating anandamide-induced CB1 receptor activation in the dorsal hippocampus. This approach may lead to new pharmacological treatments for traumatic memories and related psychiatric disorders.
- Subjects
ANANDAMIDE; CANNABINOID receptors; HYDROLASES; TRANQUILIZING drugs; FEAR; PSYCHOPHARMACOLOGY; AMIDASES; AMIDES; ANIMALS; ARACHIDONIC acid; CARRIER proteins; CELL receptors; DRUGS; HIPPOCAMPUS (Brain); MEMORY; MICE; NEUROTRANSMITTERS; SEROTONIN; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
Journal of Psychopharmacology, 2017, Vol 21, Issue 6, p750
- ISSN
0269-8811
- Publication type
journal article
- DOI
10.1177/0269881117691567