RT Conference Proceedings
T1 Pharmacogenetic inhibition of the infralimbic cortex promotes reinstatement of cocaine-context memories in mice.
A1 Pérez-Cano, Ana María
A1 Ávila-Gámiz, Fabiola
A1 Pérez Berlanga, José Manuel
A1 Santín-Núñez, Luis Javier
A1 Ladrón de Guevara-Miranda, David
K1 Drogas - Efectos fisiológicos
K1 Cocaína - Efectos fisiológicos
AB Relapse is one of the main problems concerning treatment of cocaine use disorder. It have been suggested that the infralimbic cortex (IL), a division of the medial prefrontal cortex, is involved in extinction and reinstatement of associative memories, including those involving drugs. However, more selective strategies are needed to elucidate the involvement of IL in the long-term maintenance of drug-related maladaptive behaviours. Here, we employed pharmacogenetics to assess the causal role of IL in the reinstatement of a cocaine-induced conditioned place preference (CPP). For this purpose, adult C57BL/6J mice received bilateral intra-IL microinjections of an adeno-associated viral (AAV) vector containing the hM4Di designed receptor (AAV5-CaMKII-hM4Di-mCherry; AAV-hM4Di, n=11) or a control vector (AAV5-CaMKII-mCherry; AAV-control, n=9) prior receiving training in the cocaine-induced CPP model. After habituation, animals received compartment-paired conditioning by increasing doses of cocaine (2-16 mg/kg/day, i.p.) and were tested for cocaine-CPP, after which they were subjected to forced CPP extinction and then re-tested for cocaine-CPP. On day 37 after AAV infusion, mice received Clozapine N-oxide (CNO, 5 mg/kg, i.p.) and 30 min later were tested for cocaine-primed (7.5 mg/kg, i.p.) CPP reinstatement. Ninety minutes after, animals were perfused, and brains dissected. Our results indicated that both groups acquired and subsequently extinguished cocaine-CPP. However, only the AAV-hM4Di group showed a significant preference for the cocaine-paired compartment during the CPP reinstatement test. Immunofluorescence analyses of c-Fos expression in IL revealed a decrease of ~60% in mCherry+/c-Fos+ co-labelling in the AAV-hM4Di group, suggesting reduced IL neural activity during CPP reinstatement. Therefore, our data suggests that the IL plays a causal role in relapse to cocaine-related maladaptive behaviours, highlighting its importance as a potential therapeutic target.
YR 2023
FD 2023
LK https://hdl.handle.net/10630/27688
UL https://hdl.handle.net/10630/27688
LA eng
NO Funding: PID2020-113806RB-I00, 08-2021-AREA3, B1-2020_06, FPU20/00908, PRE2018-085673, PREDOC_01094, POSTDOC_ 21_00222. II Plan Propio de Investigación, Transferencia y Divulgación Científica de la UMA.
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026