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Effects of the kappa opioid agonist U50,488 and the kappa opioid antagonist nor-binaltorphimine on choice between cocaine and food in rhesus monkeys
Authors:S.?Stevens Negus  author-information"  >  author-information__contact u-icon-before"  >  mailto:negus@mclean.harvard.edu"   title="  negus@mclean.harvard.edu"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:(1) Alcohol and Drug Abuse Research Center; Harvard Medical School, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA
Abstract:Rationale Selective kappa opioid receptor agonists usually decrease cocaine self-administration in procedures that use rate-based measures of reinforcement; however, the rate-altering effects of kappa agonists complicate interpretation of these findings.Objectives To evaluate the effects of the selective kappa agonist U50,488 and the selective kappa antagonist nor-binaltorphimine (nor-BNI) on concurrent choice between cocaine and food in rhesus monkeys. The concurrent-choice procedure provides a rate-independent measure of the relative reinforcing effects of cocaine in comparison with food.Methods Four rhesus monkeys were trained to respond under a concurrent-choice schedule for food (1-g pellets) or cocaine (0–0.1 mg/kg per injection). Saline and increasing doses of U50,488 (0.0032–0.1 mg/kg per h) were administered by pseudo-continuous i.v. infusion (one infusion every 20 min) during sequential 3-day blocks. In a separate experiment, monkeys were treated with nor-BNI (3.2 mg/kg, i.v.), and cocaine choice was re-determined during pseudo-continuous infusion with saline or U50,488 (0.1 mg/kg per h).Results During saline treatment, cocaine maintained a dose-dependent and monotonic increase in cocaine choice. Monkeys responded primarily for food when low cocaine doses were available (0–0.01 mg/kg per injection) and primarily for cocaine when higher cocaine doses were available (0.032–0.1 mg/kg per injection). U50,488 produced a dose-dependent increase in cocaine choice, manifested as leftward shifts in the cocaine-choice, dose–effect curve. U50,488 also dose-dependently decreased overall response rates. Nor-BNI did not alter cocaine choice, but it attenuated the effects of U50,488.Conclusions These results suggest that continuous treatment with U50,488 produces a kappa receptor-mediated increase in the relative reinforcing effects of cocaine in comparison with food.
Keywords:Cocaine  Choice  U50,488  Nor-binaltorphimine  Kappa opioid receptors
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