Dihydroetorphine: physical dependence and stereotypy after continuous infusion in the rat

Dose, duration, and pattern of nicotine administration as determinants of behavioral dependence in rats

“…What is not known is whether a period of regular daily tobacco use is needed to produce physiological dependence on nicotine. Studies with other dependence-producing drugs in animals suggest that physical dependence is most readily produced when drug exposures are arranged to maintain drug in the body nearly continuously for several days (Aceto et al 2000). Even daily treatment with short-acting drugs often fails to produce dependence (Aceto et al 1997), presumably because between exposures, the drug concentrations fall below a minimum needed at cellular sites critical for dependence development.…”

Discriminative stimulus and antinociceptive effects of dihydroetorphine in rhesus monkeys

“…However, in those studies, dihydroetorphine was administered intermittently, usually once daily. When dihydroetorphine was administered hourly (Tokuyama et al 1994) or continuously infused (Aceto et al 2000;Ohmori et al 2001a), dependence developed as evidenced by the emergence of withdrawal when dihydroetorphine treatment was discontinued or when the opioid antagonist naloxone was administered. Thus, while initial studies on dihydroetorphine suggested that it might be an especially useful analgesic because dependence did not appear to develop during chronic treatment, the more recent studies using more aggressive treatments failed to support the hypothesized novelty of dihydroetorphine.…”