RT Journal Article
T1 Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis
A1 Ávila-Gámiz, Fabiola
A1 Pérez-Cano, Ana M.
A1 Pérez-Berlanga, José Manuel
A1 Zambrana-Infantes, Emma N.
A1 Mañas-Padilla, María del Carmen
A1 Gil-Rodríguez, Sara
A1 Tronel, Sophie
A1 Santín-Núñez, Luis Javier
A1 Ladrón de Guevara-Miranda, David
K1 Neurobiología del desarrollo
AB Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (N = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU+ DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.
PB Elsevier
YR 2025
FD 2025-01-10
LK https://hdl.handle.net/10630/36048
UL https://hdl.handle.net/10630/36048
LA eng
NO Fabiola Ávila-Gámiz, Ana M. Pérez-Cano, José Manuel Pérez-Berlanga, Emma N. Zambrana-Infantes, M. Carmen Mañas-Padilla, Sara Gil-Rodríguez, Sophie Tronel, Luis J. Santín, David Ladrón de Guevara-Miranda, Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis, Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 136, 2025, 111148, ISSN 0278-5846, https://doi.org/10.1016/j.pnpbp.2024.111148.
NO Funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 24 ene 2026