Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats.

Autor: Soares LA; Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil., Nascimento LMM; Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil., Guimarães FS; Departamento de Farmacologia, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Gazarini L; Universidade Federal de Mato Grosso Do Sul, Três Lagoas, MS, Brazil., Bertoglio LJ; Universidade Federal de Mato Grosso Do Sul, Três Lagoas, MS, Brazil. leandro.bertoglio@ufsc.br.; Depto. de Farmacologia, CCB, UFSC, Campus Universitário S/N, Florianópolis, SC, 88049-900, Brazil. leandro.bertoglio@ufsc.br.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2024 Sep; Vol. 241 (9), pp. 1827-1840. Date of Electronic Publication: 2024 May 01.
DOI: 10.1007/s00213-024-06596-8
Abstrakt: Rationale: Therapeutic approaches to mitigating traumatic memories have often faced resistance. Exploring safe reconsolidation blockers, drugs capable of reducing the emotional valence of the memory upon brief retrieval and reactivation, emerges as a promising pharmacological strategy. Towards this objective, preclinical investigations should focus on aversive memories resulting in maladaptive outcomes and consider sex-related differences to enhance their translatability.
Objectives: After selecting a relatively high training magnitude leading to the formation of a more intense and generalized fear memory in adult female and male rats, we investigated whether two clinically approved drugs disrupting its reconsolidation remain effective.
Results: We found resistant reconsolidation impairment by the α 2 -adrenergic receptor agonist clonidine or cannabidiol, a major non-psychotomimetic Cannabis sativa component. However, pre-retrieval administration of D-cycloserine, a partial agonist at the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor complex, facilitated their impairing effects on reconsolidation. A similar reconsolidation blockade by clonidine or cannabidiol was achieved following exposure to a non-conditioned but generalized context after D-cycloserine administration. This suggests that sufficient memory destabilization can accompany generalized fear expression. Combining clonidine with cannabidiol without potentiating memory destabilization by D-cycloserine was ineffective.
Conclusions: These findings highlight the importance of NMDA receptor signaling in memory destabilization and underscore the efficacy of a dual-step pharmacological intervention in attenuating traumatic-like memories, even in a context different from the original learning environment.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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