Differential expression of response-disruptive and somatic indices of opiate withdrawal during the initiation and development of opiate dependence

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

“…For example, repeated naloxone experience in acute morphine-dependent subjects is necessary for the potentiation of naloxone potency over days of treatment at low (1.0-3.3 mg/kg) but not higher (5.6 mg/kg) doses of morphine . In addition, repeated naloxone experience is necessary when successive morphine (and hence successive naloxone) treatments are separated by long intervals (6 weeks), but not when shorter (24 h to 1 week) intervals between successive treatments are employed (Azorlosa et al 1994;Schulteis et al 1997Schulteis et al , 1999. These observations suggest the existence of both naloxone experience-dependent and naloxone experience-independent processes in the potentiation of withdrawal magnitude produced by repeated morphine exposure.…”

“…Using such an approach, a number of studies have demonstrated that even a single injection of an opioid agonist can elicit a state of "acute dependence" as measured by antagonist-precipitated withdrawal (Martin and Eades 1964;Cheney and Goldstein 1971;Wiley and Downs 1979;Jones 1980;Young 1986;Bickel et al 1988;Heishman et al 1989Heishman et al , 1990Adams and Holtzman 1990;Azorlosa et al 1994;White-Gbadebo and Holtzman 1994;Schulteis et al 1997Schulteis et al , 1999Schulteis et al , 2003Parker and Joshi 1998;Azar et al 2003). Consistent with the quantitative utility of the antagonist-precipitation method, the degree of shift in the antagonist dose-effect function to elicit a variety of somatic, physiological, and subjective signs of opioid withdrawal varies in direct proportion to the dose of agonist used to induce dependence (Jones 1980;Bickel et al 1988;Heishman et al 1989;Adams and Holtzman 1990;Schulteis et al 1997Schulteis et al , 1999Schulteis et al , 2003Azar et al 2003). In addition, studies in both human and animal models have suggested that peak signs of withdrawal in acute opioid dependence are generally observed when the antagonist is administered between 4 and 12 h post-morphine (Young 1986;Heishman et al 1989Heishman et al , 1990June et al 1995).…”

“…As one would expect if acute dependence reflected the early stages in the development of a full opioid dependence state, repeated treatments with morphine at daily or weekly intervals can progressively increase the severity of withdrawal-like signs elicited upon antagonist administration (Adams and Holtzman 1990;White-Gbadebo and Holtzman 1994;Schulteis et al 1997Schulteis et al , 1999Schulteis et al , 2003. Earlier work has demonstrated that repeated experience with naloxone (i.e.…”

“…Earlier work has demonstrated that repeated experience with naloxone (i.e. repeated withdrawal) following each morphine pretreatment is necessary to observe this shift in antagonist potency under some (Schulteis et al 1999 but not all conditions (Azorlosa et al 1994;Schulteis et al 1997Schulteis et al , 2003. For example, repeated naloxone experience in acute morphine-dependent subjects is necessary for the potentiation of naloxone potency over days of treatment at low (1.0-3.3 mg/kg) but not higher (5.6 mg/kg) doses of morphine .…”

“…Naloxone experience-independent processes presumably reflect direct neuroadaptive responses to repeat administration of morphine itself, whereas the naloxone experience-dependent processes have been suggested to reflect underlying conditioning mechanisms (Adams and Holtzman 1990;Schulteis et al 1999Schulteis et al , 2003. Wikler (1973) and others (e.g.…”