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- Title
Intravenous self-administration of etonitazene alone and combined with cocaine in rhesus monkeys: comparison with heroin and antagonism by naltrexone and naloxonazine.
- Authors
Achat-Mendes, Cindy; Valdez, Glenn; Platt, Donna; Rowlett, James; Spealman, Roger
- Abstract
In humans, μ opioid–cocaine combinations (speedballs) have been reported to heighten pleasurable effects and result in greater abuse potential compared to either drug individually. Emerging evidence in animals suggests that the ability of μ opioids to enhance the reinforcing effects of cocaine might be independent of their μ intrinsic efficacy even though μ agonist efficacy appears to be a determinant in the reinforcing effects of μ opioids themselves. This study examined the relationship between agonist efficacy, self-administration, and the enhancement of cocaine self-administration using the high-efficacy μ agonist etonitazene. Rhesus monkeys self-administered cocaine, heroin, etonitazene, and opioid–cocaine combinations under a progressive-ratio schedule of intravenous drug injection. Unlike cocaine and heroin, etonitazene did not maintain consistent self-administration at any dose tested (0.001–1.0 μg/kg/injection). However, combining etonitazene (0.1–1.0 μg/kg/injection) with cocaine (0.01 and 0.03 mg/kg/injection) enhanced cocaine self-administration, and this enhancement was attenuated by naltrexone. These effects are similar to those obtained by combining non-reinforcing doses of heroin and cocaine. Antagonism of etonitazene–cocaine and heroin–cocaine self-administration by naloxonazine was short lasting and was not maintained after 24 h (when naloxonazine’s purported μ1 subtype antagonist effects are thought to predominate). The results suggest that high μ agonist efficacy does not guarantee consistent drug self-administration and that the ability of μ agonists to enhance cocaine self-administration does not depend exclusively on reinforcing efficacy. Moreover, the results do not support a major role for μ1 receptor mechanisms in either etonitazene- or heroin-induced enhancement of cocaine self-administration.
- Subjects
DRUG abuse; ANIMAL behavior; LABORATORY monkeys; DRUGS of abuse; CHEMICAL inhibitors; DRUG antagonism
- Publication
Psychopharmacology, 2009, Vol 204, Issue 3, p489
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-009-1480-0