Novelty facilitates the persistence of aversive memory extinction by dopamine regulation in the hippocampus and ventral tegmental area

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2023-12, Vol.127, p.110832-110832, Article 110832
• Main Authors: Lima, Karine Ramires, Alves, Niege, Lopes, Luiza Freitas, Picua, Steffanie Severo, da Silva de Vargas, Liane, Daré, Leticia Rossi, Ramborger, Bruna, Roehrs, Rafael, de Gomes, Marcelo Gomes, Mello-Carpes, Pâmela Billig
• Format: Article
• Language: English
• Subjects: Behavior; Behavioral tagging; Dopaminergic system; Inhibitory avoidance; Learning
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2023.110832

Aversive memory extinction comprises a novel learning that blocks retrieving a previously formed traumatic memory. In this sense, aversive memory extinction is an excellent tool for decreasing fear responses. However, this tool it's not effective in the long term because of original memory spontaneous recovery. Thus, searching for alternative strategies that strengthen extinction learning is essential. In the current study, we evaluated the effects of a novel context (i.e., novelty) exposure on aversive memory extinction enhancement over days and the dopaminergic system requirement. Given the purpose, experiments were conducted using 3-month-old male Wistar rats. Animals were trained in inhibitory avoidance (IA). Twenty-four hours later, rats were submitted to a weak extinction protocol. Still, 30 min before the first extinction session, animals were submitted to an exploration of a novel context for 5 min. After, memory retention and persistence were evaluated 24 h, 3, 7, 14, and 21 days later. The exposition of a novel context caused a decrease in aversive responses in all days analyzed and an increase in dopamine levels in the hippocampus. The intrahippocampal infusion of dopamine in the CA1 area or the stimulation of the ventral tegmental area (VTA) by a glutamatergic agonist (NMDA) showed similar effects of novelty. In contrast, VTA inhibition by a gabaergic agonist (muscimol) impaired the persistence of extinction learning induced by novelty exposition and caused a decrease in hippocampal dopamine levels. In summary, we show that novel context exposure promotes persistent aversive memory extinction, revealing the significant role of the dopaminergic system. •Novelty exposure as a non-pharmacological tool for aversive memory extinction.•Intrahippocampal dopamine infusion mimics the effects of novelty on memory extinction.•VTA modulates the persistence of aversive memory extinction.•Novelty and VTA stimulation increase the catecholamine levels in the hippocampus.