Methocinnamox (MCAM) antagonizes the behavioral suppressant effects of morphine without impairing delayed matching-to-sample accuracy in rhesus monkeys

Vanessa Minervini, Alex Disney, Stephen M. Husbands, Charles P. France

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)


Rationale: Opioid abuse remains a serious public health problem. The pseudoirreversible mu opioid receptor antagonist methocinnamox (MCAM) might be useful for treating opioid abuse and overdose. Because endogenous opioid systems can modulate cognition and decision-making, it is important to evaluate whether long-term blockade of mu opioid receptors by MCAM adversely impacts complex operant behavior involving memory. Objective: This study tested the effects of MCAM in rhesus monkeys responding under a delayed matching-to-sample task, with correct responses reinforced by sucrose pellets. Because MCAM did not alter performance, antagonism of the rate-decreasing effects of morphine was used to confirm that an effective dose of MCAM was administered. Moreover, the muscarinic receptor antagonist scopolamine and the N-methyl-D-aspartate antagonist phencyclidine were studied as positive controls to demonstrate sensitivity of this procedure to memory disruption. Results: Neither MCAM (0.32 mg/kg) nor morphine (1–5.6 mg/kg) impaired delayed matching-to-sample accuracy. Morphine dose-dependently decreased the number of trials completed before MCAM administration, and a single injection of MCAM blocked the behavioral suppressant effects of morphine for at least 7 days. Scopolamine (0.01–0.056 mg/kg) and phencyclidine (0.1–0.56 mg/kg) dose-dependently decreased delayed matching-to-sample accuracy and the number of trials completed. Conclusions: MCAM did not impair memory (as measured by accuracy in a delayed matching-to-sample task) and did not decrease responding for or consumption of sucrose pellets. This dose of MCAM attenuates self-administration of opioids and reverses as well as prevents opioid-induced respiratory depression. These results provide further support for a favorable adverse effect profile for MCAM.

Original languageEnglish
Pages (from-to)3057–3065
Early online date9 Aug 2020
Publication statusPublished - 31 Oct 2020


  • Antagonism
  • Cognition
  • Memory
  • Operant behavior
  • Opioid
  • Rhesus monkey

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Methocinnamox (MCAM) antagonizes the behavioral suppressant effects of morphine without impairing delayed matching-to-sample accuracy in rhesus monkeys'. Together they form a unique fingerprint.

Cite this