TY - JOUR T1 - Behavioral Effects of Opioid Full and Partial Agonists During Chronic Buprenorphine Treatment. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.259010 SP - jpet.119.259010 AU - Sarah L Withey AU - Roger D Spealman AU - Jack Bergman AU - Carol A Paronis Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/early/2019/08/14/jpet.119.259010.abstract N2 - Buprenorphine, a partial agonist at the μ-opioid receptor, is commonly prescribed for the management of opioid addiction. It is thought to forestall relapse by preventing withdrawal sickness (agonist action) and, as well, reducing the relapse-related effects of abused opioids such as heroin or fentanyl (antagonist action). Notwithstanding buprenorphine's clinical popularity, the relationship between its effectiveness in attenuating relapse-related behavior and its opioid efficacy is poorly understood. Furthermore, changes in the antinociceptive potency or effectiveness of opioid drugs that might occur during buprenorphine treatment have not been characterized. Here, we address these questions by assessing the ability of daily buprenorphine treatment to protect against the reinstatement of drug-seeking behavior by opioids differing in efficacy and, in separate experiments, by determining how such treatment may modify their antinociceptive effects. In one set of experiments, squirrel monkeys were trained to respond under a drug/food choice procedure (i.e., concurrent fixed ratio (FR) schedules of i.v. oxycodone and milk delivery). Next, the priming strength of different opioids during sessions in which saline, rather than oxycodone, was available for i.v. self-administration, was determined before and during chronic buprenorphine treatment (0.1 or 0.32 mg/kg/day). In a second group of subjects, the antinociceptive effects of the different opioids were assessed before and during chronic buprenorphine treatment. Results show that, notwithstanding some tolerance, full agonists retain high efficacy in producing priming and antinociceptive effects. In contrast, both the priming strength and antinociceptive effectiveness of partial agonists were decreased. These results suggest that the utility of buprenorphine in the management of opioid addiction and how it alters the analgesic effects of opioids can vary depending on the efficacy of the abused or prescribed opioids.SIGNIFICANCE STATEMENT Our findings indicate that the pharmacological efficacy of abused opioids may predict the ability of buprenorphine to attenuate their relapse-related priming and analgesia-related antinociceptive effects. This information can help inform the choice of pharmacotherapy for opioid addiction, i.e., buprenorphine vs. methadone or naltrexone. ER -