Context-specific morphine tolerance and withdrawal: The effects of interdose interval

Intra-Administration Associations and Withdrawal Symptoms: Morphine-Elicited Morphine Withdrawal.

“…Although there was no difference between groups in the frequency of rearing, it should be noted that there is some controversy concerning the efficacy of rearing as a measure of morphine withdrawal. There are studies of associative contributions to morphine withdrawal that have used this rearing measure (e.g., Azorlosa, Hartley, & Deffner-Rappold, 1994; Deffner-Rappold, Azorlosa, & Baker, 1996; Kelsey, Aranow, & Matthews, 1990); however McDonald and Siegel (1998) provided evidence suggesting that rearing in morphine-experienced rats is a manifestation of novelty-elicited exploration rather than morphine withdrawal (but see Azorlosa & Simmons, 1999).…”

“…Such findings are relevant for interpreting some apparently conflicting findings in the literature. Although there are many reports that withdrawal symptoms are especially pronounced in the presence of drug-paired environmental cues (e.g., Azorlosa et al., 1994; Deffner-Rappold et al, 1996; Kelsey et al, 1990), there are some reports to the contrary; that is, it has been suggested that morphine withdrawal symptoms are not more pronounced in the drug-paired environment than in an alternative environment (Sobrero & Bouton, 1989; Zellner, Dacanay, & Riley, 1984). Such findings typically have been interpreted as evidence contrary to an associative analysis of withdrawal symptoms: “These results [transenvironmental withdrawal symptoms] lead us to suggest that withdrawal responses are not compensatory conditioned responses elicited by drug-associated cues” (Zellner et al, 1984, p. 179).…”

Coordinated activity of a central pathway drives associative opioid analgesic tolerance

“…Accumulating evidence has emerged to suggest that learning processes play an essential role in the development of tolerance to the analgesic effect of opioids. For instance, a large amount of animal studies show that rodents administered with morphine in a distinctive context displayed a higher degree of morphine tolerance than the animals given morphine in a home cage (14)(15)(16)(17)(18)(19)(20). This associative opioid analgesic tolerance (AOAT) can also make a clinical impact on the analgesic efficacy in the treatment of patients with chronic pain (21).…”