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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.
J Psychopharmacol. 2017 06; 31(6):750-756.JP

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.

Authors+Show Affiliations

1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.2 Department of Pharmacology, Medical School of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.3 Max Planck Institute of Psychiatry, Munich, Germany.1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28583049

Citation

Gobira, Pedro H., et al. "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." Journal of Psychopharmacology (Oxford, England), vol. 31, no. 6, 2017, pp. 750-756.
Gobira PH, Lima IV, Batista LA, et al. 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. J Psychopharmacol. 2017;31(6):750-756.
Gobira, P. H., Lima, I. V., Batista, L. A., de Oliveira, A. C., Resstel, L. B., Wotjak, C. T., Aguiar, D. C., & Moreira, F. A. (2017). 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. Journal of Psychopharmacology (Oxford, England), 31(6), 750-756. https://doi.org/10.1177/0269881117691567
Gobira PH, et al. 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. J Psychopharmacol. 2017;31(6):750-756. PubMed PMID: 28583049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Gobira,Pedro H, AU - Lima,Isabel V, AU - Batista,Luara A, AU - de Oliveira,Antônio C, AU - Resstel,Leonardo B, AU - Wotjak,Carsten T, AU - Aguiar,Daniele C, AU - Moreira,Fabricio A, Y1 - 2017/02/21/ PY - 2017/6/7/entrez PY - 2017/6/7/pubmed PY - 2018/3/23/medline KW - AA-5-HT KW - Endocannabinoid system KW - TRPV1 KW - anandamide KW - contextual fear conditioning SP - 750 EP - 756 JF - Journal of psychopharmacology (Oxford, England) JO - J Psychopharmacol VL - 31 IS - 6 N2 - 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. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/28583049/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_ L2 - https://journals.sagepub.com/doi/10.1177/0269881117691567?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -