Oral Oxycodone Self Administration in Rats with a History of Responding Under a Multiple Schedule for Ethanol and Food or Oxycodone and Food

Abstract ID 97121 Poster Board 110 For people who struggle with alcohol-use disorder (AUD) or opioid-use disorder (OUD), the co-administration of other abused substances, or polysubstance abuse, is common. However, preclinical studies that assess the co-administration of abused substances are complicated by a number of variables including the respective routes of administration, time course of the substances, and history of use with each substance. Previous research from this laboratory has shown that food pellets and ethanol (18 or 32% v/v) can be self administered by rats under a multiple schedule. We, therefore, expanded these studies to examine whether rats trained to orally self administer food and ethanol (18% v/v) or food and oxycodone (1 mg/ml) would differentially self administer oxycodone (0.3-3.2 mg/ml). Additionally, we investigated the effects of the opioid receptor antagonist naltrexone (1 and 3.2 mg/kg, ip) on the self administration of all three reinforcers (i.e., food, ethanol, and oxycodone). During these sessions, overall response rate, pre-ratio pausing (PRP), and completed fixed ratios were recorded as dependent measures. Blood ethanol concentrations (BECs) were collected when subjects met the stability criterion for ethanol substitutions. Our results indicated that response rates for food were significantly higher than those for either oral alcohol or oral oxycodone administration, and that these high response rates were maintained irrespective of the concentration of oxycodone presented. In contrast, and regardless of subject9s training history with alcohol or oxycodone, increasing the oxycodone concentration presented under the multiple schedule significantly decreased response rates for oxycodone and the number of completed fixed ratios, while significantly increasing overall intake. When naltrexone was administered prior to responding under the multiple schedule with the training concentrations of ethanol or oxycodone, response rate, PRP, and completed fixed ratios for food or drug (ethanol or oxycodone) presentation was not affected irrespective of training history. However, both doses of naltrexone significantly decreased BEC compared to water but had no significant effect on oxycodone intake (i.e., there were some increases and decreases). Taken together, these data indicated that responding for increasing concentrations of oral oxycodone was not significantly affected by a prior history of training with either ethanol or oxycodone in male rats. The present experiments also found that naltrexone (i.p.) was more effective at significantly and uniformly decreasing BEC than oxycodone intake. Finally, to what extent these effects with ethanol and oxycodone are specific to oral self administration, and the respective pharmacokinetics of this route, needs to be investigated further.