Data Repository for Unique response patterns and high reinforcing efficacy characterize self-administration of combined fentanyl and methamphetamine

Background: Recent clinical data indicates that combined use of fentanyl and methamphetamine (FENT+METH) is climbing, leading to increased adverse health events and deaths. Despite this, preclinical research has not extensively characterized the behavioral patterns associated with combined FENT+METH in rodent models.Methods: The present study assessed lever press behavior under LgA (6 hour, FR1) to characterize response patterns for fentanyl (FENT), methamphetamine (METH), and FENT+METH in male and female Long Evans rats. Further, progressive ratio (PR) responding was used to compare the rewarding efficacy of FENT+METH to FENT and METH alone.Results: Female FENT animals displayed the greatest LgA responding, while males did not show differences between drugs. In both sexes, FENT+METH produced distinct response patterns when compared to FENT or METH alone. Animals self-administering single drugs displayed ‘burst-like’ responding, with mostly grouped infusions and more time between infusion events, while FENT+METH animals produced mostly individual, evenly spaced infusions. We also found that FENT+METH animals produced perseverative behavior during extinction, with males failing to reach extinction criteria. METH alone engendered greater responding under drug-induced reinstatement. Further, FENT+METH had greater reinforcing efficacy than FENT or METH alone, which may account for the observed changes in response patterns, as enhanced efficacy may result in fewer infusions needed in rapid succession to reach preferred drug levels.Conclusions: The present findings highlight the unique response patterns and increased rewarding efficacy produced by FENT+METH, which may engender a more ‘hazardous’ behavioral phenotype.