Drug repurposing of riluzole attenuates acquisition, accelerates extinction, and prevents reinstatement of ethanol-induced conditioned place preference
Psychopharmacology, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s00213-026-07178-6
- Dergi Adı: Psychopharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, MEDLINE, Psycinfo, SportDiscus, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Psychology & Behavioral Sciences Collection (EBSCO)
- Anahtar Kelimeler: Alcohol use disorder, Conditioned place preference, Drug repurposing, Glutamatergic neurotransmission, Relapse-like behavior, Riluzole
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Background: Alcohol use disorder (AUD) is associated with persistent drug-related memories that lead to relapse. Glutamatergic dysregulation plays a critical role in the acquisition, extinction, and reinstatement of alcohol. Riluzole, a glutamate-modulating agent, has been suggested to influence these processes; however, its effects on ethanol-related contextual learning are not fully defined. Methods: Male Swiss albino mice (25–30 g) were used in a biased conditioned place preference (CPP) model to evaluate the effects of riluzole on ethanol-induced acquisition, extinction and reinstatement in mice. Animals were conditioned with ethanol (2.0 g/kg, i.p). Riluzole (3, 10, or 30 mg/kg, i.p.) was given 30 min before ethanol administration. Extinction and reinstatement phase was conducted by using separate cohort. The ability of riluzole to prevent reinstatement was then assessed using a low priming dose of ethanol (0.5 g/kg, i.p.). CPP was quantified as the time spent in the drug-paired compartment. Results: Ethanol produced a strong CPP and confirmed the successful acquisition of drug-context associations. Riluzole did not significantly alter acquisition at low doses (3 and 10 mg/kg), but a modest effect was observed at the highest dose (30 mg/kg). During extinction, riluzole facilitated a time-dependent reduction in CPP. Riluzole 10 and 30 mg/kg, increased extinction learning. In the reinstatement phase, ethanol pre-treatment significantly induced CPP, whereas riluzole reduced this effect at 10 and 30 mg/kg and showed no significant reducing effect at 3 mg/kg. Conclusions: Riluzole attenuated ethanol-induced CPP, facilitated extinction, and reduced reinstatement in a dose and phase-dependent manner. These findings demonstrate that riluzole influences multiple phases of ethanol-associated conditioned behavior and support its further investigation as a potential pharmacological strategy for alcohol use disorder.