RMTG MOLECULAR ADAPTATIONS IN RELATION TO COCAINE-SEEKING AFTER LONG OR INTERMITTENT ACCESS TO THE DRUG IN RATS

Cocaine addiction becomes a major public health concern in Europe due to increasing availability and consumption. Despite advances in understanding the brain reward system’s involvement in this pathology, molecular adaptations occurring in brain regions known to regulate this system, such as the rostromedial tegmental nucleus (RMTg) which exerts a strong inhibitory control over dopaminergic neurons of the ventral tegmental area, still deserve investigations. To assess potential gene expression changes in RMTg induced by cocaine seeking after intravenous cocaine self-administration (iCSA), male rats surgically implanted with intravenous catheter are trained for a few days to perform nose-poke (NP) iCSA under a conventional schedule of reinforcement (Standard Access, SdA). Afterwards, they are divided for three weeks to intermittent (IntA) or long access (LgA) schedules of iCSA, known to induce distinct reinforcement-related adaptations and to better capture behavioral signs of loss of control over cocaine consumption, in addition to SdA. After a withdrawal period of three weeks, animals are submitted to a ‘’double’ cocaine-seeking session during which NP activity is recorded after exposing them to cocaine-associated cues in the operant context, then to the drug itself. Immediately after the cocaine-seeking session, RMTg and other brain structures of the reward system are rapidly collected for comparisons of molecular gene expression between the different groups (including a saline self-administering control group). Differential gene expression in RMTg and brain reward regions will reveal specific molecular signatures of cocaine-seeking after IntA and LgA schedules of reinforcement, suggesting new lines of research in cocaine addiction research.