Efficacy Related Modulation of Behavioral Effects of Opioids During Chronic Buprenorphine Treatment in Squirrel Monkeys

Abstract

Opioid addiction is characterized as a chronic relapsing disorder in which renewed drug‐seeking behavior during abstinence can be provoked by exposure to an opioid or opioid‐associated cues. In laboratory subjects, drug‐seeking behavior similarly can be reinstated by priming with the drug or drug‐related stimuli. Buprenorphine (BUP), a partial agonist at the μ opioid receptor, is commonly prescribed for the management of opioid addiction but its ability to reduce reinstatement behavior in laboratory subjects is not well understood. In the present studies, squirrel monkeys (n=4) were trained to respond under a drug/food choice procedure (i.e., concurrent FR schedules of i.v. oxycodone and milk delivery). Next, the priming strength (i.e., % injection lever responding when the choice was between i.v. saline or milk) of different opioids was determined before and during chronic BUP treatment (0.1 or 0.32 mg/kg/day). Results thus far indicate that: 1) despite decreased potency, indicative of tolerance, full agonists (oxycodone, methadone) maintain priming strength during chronic treatment whereas 2) the priming strength of partial agonists (nalbuphine, butorphanol) is dramatically decreased. These results suggest a reduction in the ability of lower efficacy, but not high efficacy agonists to provoke relapse in BUP‐maintained people. The extent to which these findings may reflect efficacy‐related differences in other opioid endpoints (e.g. analgesia) during BUP maintenance remains to be determined.Support or Funding InformationFunded by NIH/NIDA: DA035857