SODIUM OXYBATE ATTENUATES ALCOHOL AND COCAINE CO-ADMINISTRATION IN A NOVEL MODEL OF POLYDRUG USE IN ALCOHOL PREFERRING MSP RATS

Polydrug use is a public health concern that, despite its substantial clinical and social relevance, has been relatively understudied in preclinical research. This gap is largely due to the challenges associated with modelling human polydrug-taking behaviours in laboratory animals. Here, we describe a novel operant self-administration procedure to study cocaine and alcohol co-abuse in genetically selected alcohol-preferring Marchigian Sardinian (msP) rats. In this context, we also assessed the effects of sodium oxybate.
Male and female msP rats were trained to oral 30-min 10% alcohol self-administration (FR1) or to 2h intravenous cocaine. Rats then received oral sodium oxybate (0, 100, 300, 600 mg/kg), with an additional 750 mg/kg dose in males. Sodium oxybate attenuated both acute and chronic alcohol and cocaine self-administration at doses of 600 mg/kg in females and 750 mg/kg in males.
Next, we developed a self-administration model to investigate the effect of sodium oxybate when alcohol and cocaine were both available. For this purpose, rats were trained to receive alcohol by pressing one lever and cocaine by pressing the alternative lever. During the 2h sessions the two levers were alternatively reinforced (intervals: 5 min cocaine under FR5 followed by 10 min alcohol FR1). Results showed that sodium oxybate (600 mg/kg) significantly reduced the consumption of both substances.
This study describes a novel self-administration model for investigating the concurrent use of cocaine and alcohol in msP rats and demonstrates that sodium oxybate significantly reduces the intake of both substances during co-abuse. NIH/NIAAA AA014351; AA017447, PRIN-PNRR2022(P202274WPN), PRIN-2022(20227HRFPJ); MNESYS(PE0000006)-AMSUD2024.