Effects of the kappa opioid antagonist nor‐binaltorphimine on cocaine vs. food choice and extended‐access cocaine intake in rhesus monkeys (658.6)

Abstract

The dynorphin/κ opioid receptor system (KOR) has been implicated as one potential neurobiological target for treating cocaine addiction. This study determined effects of the KOR antagonist nor‐binaltorphimine (nor‐BNI) on cocaine self‐administration by rhesus monkeys responding under a novel procedure that featured two daily components: (1) 2‐h choice sessions (9‐11am) when monkeys could choose between food pellets and cocaine (0‐0.1 mg/kg/inj, IV), and (2) 20‐h “extended access” sessions (noon‐8am) when only cocaine (0.1 mg/kg/inj) was available under a fixed‐ratio schedule to promote high daily cocaine intakes. After 14 days of responding under this novel procedure, nor‐BNI (3.2 mg/kg, IM) was administered, and responding was evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained a dose‐dependent increase in cocaine choice, and monkeys also self‐administered cocaine throughout the extended access component. Total daily intake averaged 7.5±0.66 mg/kg cocaine. Nor‐BNI treatment had no significant effect on cocaine choice either during or after withdrawal from extended cocaine access. These results suggest the dynorphin/KOR system does not play a major role in cocaine self‐administration under these conditions. These results also do not support the utility of KOR antagonists as medications to treat ongoing cocaine use in persons dependent on cocaine.Grant Funding Source: Funded by NIH grant R01DA026946.