STUDY OF PERIPHERAL INFLAMMATION AND SEX DIFFERENCES IN COCAINE ADDICTION-LIKE BEHAVIOUR USING THE THREE-CRITERIA MODEL

Cocaine addiction is a major public health concern associated with neuroplastic changes and neuroinflammation. Indeed, prolonged drug exposure can trigger the release of pro-inflammatory cytokines and other signalling molecules known to be stimulated by cocaine or to modulate its rewarding effects. This study investigates the predictive role of inflammatory events in a rat model of cocaine addiction, focusing on sex-dependent differences.
Male and female Sprague–Dawley rats were subjected to an acute cocaine challenge (4 mg/kg i.v.). Plasma samples were collected to quantify pro-inflammatory cytokines in order to characterize the peripheral inflammatory profile and explore its association with vulnerability to addiction. Subsequently, animals underwent an intravenous cocaine self-administration protocol based on the three-criteria model (Deroche-Gamonet, Belin and Piazza, 2004), allowing classification according to addiction vulnerability based on seeking persistence, motivation for cocaine, and compulsive drug seeking.
Preliminary results show a progressive increase in active versus inactive lever responding in both sexes, indicating stable acquisition of cocaine self-administration, with a higher rate of active responses in females during FR1. The three-criteria model identified animals with greater vulnerability to addiction, but there were no differences in the proportion of male and females in 0 vs 3 criteria groups. At the peripheral level, a significant increase in TNF-α and CXCL1 was detected following the cocaine challenge, with no sex-dependent differences. Our preliminary analysis does not suggest predictive value of either cytokine.
This study identifies cocaine-induced peripheral inflammatory responses which could be associated with vulnerability to addiction, an issue that requires further investigation.