Handling and novel object recognition modulate fear response and endocannabinoid signaling in nucleus basalis magnocellularis
Bengoetxea de Tena, Iker (Universidad del País Vasco)
Moreno-Rodríguez, Marta (Universidad del País Vasco)
Llorente-Ovejero, Alberto (Universidad del País Vasco)
Monge-Benito, Sergio (Universidad del País Vasco)
Martínez-Gardeazabal, Jonatan (Universidad del País Vasco)
Onandia-Hinchado, Iban (Universidad del País Vasco)
Manuel, Ivan (Universidad del País Vasco)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Rodríguez-Puertas, Rafael (Universidad del País Vasco)

Data:	2022
Resum:	Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naïve rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.
Ajuts:	Instituto de Salud Carlos III PI20/00153
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aversive memory ; CB1 mediated-signaling ; Cholinergic receptors ; Functional autoradiography ; Passive avoidance
Publicat a:	European Journal of Neuroscience, Vol. 55 Núm. 6 (march 2022) , p. 1532-1546, ISSN 1460-9568

DOI: 10.1111/ejn.15642
PMID: 35266590

15 p, 6.9 MB

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