ArticlePsychopharmacology2026
Drug repurposing of riluzole attenuates acquisition, accelerates extinction, and prevents reinstatement of ethanol-induced conditioned place preference.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlcohol 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.
methodsMale 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.
resultsEthanol 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.
conclusionsRiluzole 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.
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