Classically Conditioning the Response Profile of Morphine to Reduce Behavioral Dependence Withdrawal in Male Sprague-Dawley Rats

Abstract:

The opioid epidemic continues to worsen across the United States. As more individuals continue to fall victim to substance use disorders, it is becoming even more paramount that we identify possible therapies to help those struggling towards rehabilitation. This study aims to determine whether utilizing both contextual and discrete cues through classical conditioning could be a viable method to reduce withdrawal symptoms both during and after rehabilitation. Twice daily 10 mg/kg subcutaneous morphine administration was given to male Sprague-Dawley rats until behavioral tolerance thresholds were met in operant chambers responding for water. Withdrawal symptoms were measured based on changes in completed lever response sets, grooming behaviors, defecation amount, and mass — compared to baseline measures prior to drug exposure. Three groups were maintained for this study: a no-cue control which received no exposure to the conditioned stimuli (CS) during withdrawal, a context-cue-only experimental group which was only exposed to the contextual CS of the injection room, and an all-cue experimental group which was exposed to both the contextual CS and received a saline injection functioning as the discrete CS. Statistical analysis across the five days of withdrawal indicate two separate results. For completed response sets, a significant difference (p=0.122) was observed across the 5 days of withdrawal, with the context-cue group having a significantly greater number of responses during withdrawal when compared to baseline: indicating a drug-opposite response. In terms of defecation behavior, a significant difference (p=0.154) was observed between the averages of defecation during the withdrawal period compared to the baseline, with the all-cue group having very little change from baseline, indicating a drug-like response. No significant difference was observed in grooming behaviors or night mass across the withdrawal period. These initial results should be used to encourage research with larger sample sizes to investigate this concept further, in order to identify its applicability to human subjects.