Acute and chronic effects of ramelteon in rhesus monkeys (Macaca mulatta): Dependence liability studies

Charles P. France, Robert H. Weltman, Wouter Koek, Christopher M. Cruź, Lance R. McMahon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The acute and chronic effects of ramelteon, an MT-sub-1/MT-sub-2 receptor agonist, were evaluated in rhesus monkeys (Macaca mulatta) to assess discriminative stimulus effects in comparison with traditional benzodiazepine receptor agonists and to assess physical dependence potential. Discriminative effects of ramelteon were compared with midazolam in untreated monkeys and in diazepam-dependent monkeys that discriminated flumazenil. Dependence potential of ramelteon after daily 1-year administration (and intermittent discontinuation) was evaluated with standard operant procedures. Ramelteon did not produce benzodiazepine-like discriminative stimulus effects at doses up to 10 mg/kg. Long-term treatment or its discontinuation had no significant effect on spontaneous behavior, operant behavior, body weight, motor activity, or posture. These findings suggest that ramelteon is not likely to have benzodiazepine-like abuse or dependence liability.

Original languageEnglish (US)
Pages (from-to)535-541
Number of pages7
JournalBehavioral Neuroscience
Issue number3
StatePublished - Jun 2006


  • Abuse liability
  • Benzodiazepine receptor agonist
  • Dependence
  • Long term

ASJC Scopus subject areas

  • Behavioral Neuroscience


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