Extinction of avoidance behavior by safety learning depends on
endocannabinoid signaling in the hippocampus

J 2017

Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus

MICALE, Vincenzo; J. STEPAN; A. JURIK; F.A. PAMPLONA; R. MARSCH et al.

Základní údaje

Originální název

Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus

Autoři

MICALE, Vincenzo; J. STEPAN; A. JURIK; F.A. PAMPLONA; R. MARSCH; F. DRAGO; M. EDER a C.T. WOTJAK

Vydání

Journal of Psychiatric Research, OXFORD, Elsevier, 2017, 0022-3956

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30215 Psychiatry

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.000

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00100387

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Avoidance behavior; Response extinction; CB1 receptors; Dopamine D1 receptors; AM404

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 3. 2018 15:20, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

The development of exaggerated avoidance behavior is largely responsible for the decreased quality of life in patients suffering from anxiety disorders. Studies using animal models have contributed to the understanding of the neural mechanisms underlying the acquisition of avoidance responses. However, much less is known about its extinction. Here we provide evidence in mice that learning about the safety of an environment (i.e., safety learning) rather than repeated execution of the avoided response in absence of negative consequences (i.e., response extinction) allowed the animals to overcome their avoidance behavior in a step-down avoidance task. This process was context-dependent and could be blocked by pharmacological (3 mg/kg, s.c.; SR141716) or genetic (lack of cannabinoid CB1 receptors in neurons expressing dopamine D1 receptors) inactivation of CB1 receptors. In turn, the endocannabinoid reuptake inhibitor AM404 (3 mg/kg, i.p.) facilitated safety learning in a CBI-dependent manner and attenuated the relapse of avoidance behavior 28 days after conditioning. Safety learning crucially depended on endocannabinoid signaling at level of the hippocampus, since intrahippocampal SR141716 treatment impaired, whereas AM404 facilitated safety learning. Other than AM404, treatment with diazepam (1 mg/kg, i.p.) impaired safety learning. Drug effects on behavior were directly mirrored by drug effects on evoked activity propagation through the hippocampal trisynaptic circuit in brain slices: As revealed by voltage-sensitive dye imaging, diazepam impaired whereas AM404 facilitated activity propagation to CA1 in a CB1-dependent manner. In line with this, systemic AM404 enhanced safety learning-induced expression of Egr1 at level of CA1. Together, our data render it likely that AM404 promotes safety learning by enhancing information flow through the trisynaptic circuit to CA1. (C) 2017 Elsevier Ltd. All rights reserved.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

MICALE, Vincenzo; J. STEPAN; A. JURIK; F.A. PAMPLONA; R. MARSCH; F. DRAGO; M. EDER a C.T. WOTJAK. Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus. Journal of Psychiatric Research. OXFORD: Elsevier, 2017, roč. 90, JUL, s. 46-59. ISSN 0022-3956. Dostupné z: https://doi.org/10.1016/j.jpsychires.2017.02.002.

@article{1411316,
   author = {Micale, Vincenzo and Stepan, J. and Jurik, A. and Pamplona, F.A. and Marsch, R. and Drago, F. and Eder, M. and Wotjak, C.T.},
   article_location = {OXFORD},
   article_number = {JUL},
   doi = {https://doi.org/10.1016/j.jpsychires.2017.02.002},
   keywords = {Avoidance behavior; Response extinction; CB1 receptors; Dopamine D1 receptors; AM404},
   language = {eng},
   issn = {0022-3956},
   journal = {Journal of Psychiatric Research},
   title = {Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus},
   url = {https://www.sciencedirect.com/science/article/pii/S0022395616308469?via%3Dihub},
   volume = {90},
   year = {2017}
}

TY  - JOUR
ID  - 1411316
AU  - Micale, Vincenzo - Stepan, J. - Jurik, A. - Pamplona, F.A. - Marsch, R. - Drago, F. - Eder, M. - Wotjak, C.T.
PY  - 2017
TI  - Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus
JF  - Journal of Psychiatric Research
VL  - 90
IS  - JUL
SP  - 46-59
EP  - 46-59
PB  - Elsevier
SN  - 00223956
KW  - Avoidance behavior
KW  - Response extinction
KW  - CB1 receptors
KW  - Dopamine D1 receptors
KW  - AM404
UR  - https://www.sciencedirect.com/science/article/pii/S0022395616308469?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0022395616308469?via%3Dihub
N2  - The development of exaggerated avoidance behavior is largely responsible for the decreased quality of life in patients suffering from anxiety disorders. Studies using animal models have contributed to the understanding of the neural mechanisms underlying the acquisition of avoidance responses. However, much less is known about its extinction. Here we provide evidence in mice that learning about the safety of an environment (i.e., safety learning) rather than repeated execution of the avoided response in absence of negative consequences (i.e., response extinction) allowed the animals to overcome their avoidance behavior in a step-down avoidance task. This process was context-dependent and could be blocked by pharmacological (3 mg/kg, s.c.; SR141716) or genetic (lack of cannabinoid CB1 receptors in neurons expressing dopamine D1 receptors) inactivation of CB1 receptors. In turn, the endocannabinoid reuptake inhibitor AM404 (3 mg/kg, i.p.) facilitated safety learning in a CBI-dependent manner and attenuated the relapse of avoidance behavior 28 days after conditioning. Safety learning crucially depended on endocannabinoid signaling at level of the hippocampus, since intrahippocampal SR141716 treatment impaired, whereas AM404 facilitated safety learning. Other than AM404, treatment with diazepam (1 mg/kg, i.p.) impaired safety learning. Drug effects on behavior were directly mirrored by drug effects on evoked activity propagation through the hippocampal trisynaptic circuit in brain slices: As revealed by voltage-sensitive dye imaging, diazepam impaired whereas AM404 facilitated activity propagation to CA1 in a CB1-dependent manner. In line with this, systemic AM404 enhanced safety learning-induced expression of Egr1 at level of CA1. Together, our data render it likely that AM404 promotes safety learning by enhancing information flow through the trisynaptic circuit to CA1. (C) 2017 Elsevier Ltd. All rights reserved.
ER  -

MICALE, Vincenzo; J. STEPAN; A. JURIK; F.A. PAMPLONA; R. MARSCH; F. DRAGO; M. EDER a C.T. WOTJAK. Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the hippocampus. \textit{Journal of Psychiatric Research}. OXFORD: Elsevier, 2017, roč.~90, JUL, s.~46-59. ISSN~0022-3956. Dostupné z: https://doi.org/10.1016/j.jpsychires.2017.02.002.

Přehled o publikaci