Once is too much: Early development of the opponent process in taste reactivity behavior is associated with later escalation of cocaine self-administration in rats

•Some rats exhibit greater aversive taste reactivity to a cocaine-paired cue.•Greater conditioned aversive taste reactivity can occur immediately.•Greater conditioned aversive taste reactivity predicts escalation of drug taking.•Early onset of this opponent process predicts later vulnerability to drug. Evidence suggests that the addiction process may begin immediately in some vulnerable subjects. Specifically, some rats have been shown to exhibit aversive taste reactivity (gapes) following the intraoral delivery of a cocaine-predictive taste cue after as few as 1–2 taste-drug pairings. After only 3–4 trials, the number of gapes becomes a reliable predictor of later cocaine self-administration. Given that escalation of drug-taking behavior over time is recognized as a key feature of substance use disorder (SUD) and addiction, the present study examined the relationship between early aversion to the cocaine-predictive flavor cue and later escalation of cocaine self-administration in an extended-access paradigm. The data show that rats who exhibit the greatest conditioned aversion early in training to the intraorally delivered cocaine-paired cue exhibit the greatest escalation of cocaine self-administration over 15 extended-access trials. This finding suggests that early onset of the conditioned opponent process (i.e., the near immediate shift from ingestion to rejection of the drug-paired cue) is a reliable predictor of future vulnerability and resilience to cocaine addiction-like behavior. Future studies must determine the underlying neural mechanisms associated with this early transition and, hence, with early vulnerability to the later development of SUD and addiction. In so doing, we shall be in position to discover novel diagnostics and novel avenues of prevention and treatment.