Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats

Binsack, Ralf; Zheng, Minglan; Zhang, Zhan-sai; Liu, Yang; Zhu, Yimin

doi:10.1631/jzus.2006.b0892

Cited by 8 publications

(5 citation statements)

References 28 publications

(50 reference statements)

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“…These results were not unexpected, as chronic opioid agonist administration has previously been shown to decrease body weight (Binsack et al 2006; Levine et al 1998; Li et al 2010; Mitzelfelt et al 2011), and suggest that fentanyl has a greater effect on older individuals than younger individuals, which is a concern in a clinical setting.…”

Section: Discussionmentioning

confidence: 51%

Thermal sensitivity across ages and during chronic fentanyl administration in rats

2013

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Rationale Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Results Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.

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Section: Discussionmentioning

confidence: 51%

Thermal sensitivity across ages and during chronic fentanyl administration in rats

2013

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“…Bodnar, 2004), and in general it is known that acute administration of opioid agonists increases food consumption in rats (Sanger & McCarthy, 1981) while opioid antagonists decrease food consumption (Glass et al, 1999; McLaughlin & Baile, 1983; Yuan et al, 2009). However, studies looking at chronic administration of morphine show decreases in food intake and body weight (Binsack et al, 2006; Levine et al, 1988; Li et al, 2010), while chronic opioid antagonist administration increases food consumption and weight gain (Chen et al, 2004). As hypothesized, chronic fentanyl administration resulted in a decreased food consumption within the first week, and animals became tolerant to this effect as food consumption had returned to baseline after four weeks of fentanyl administration.…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic fentanyl administration on physical performance of aged rats

Mitzelfelt

DuPree

Seo

et al. 2011

Experimental Gerontology

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There is growing concern over the increasing use of opioids to treat chronic pain in the elderly primarily because of the potential increased sensitivity to the adverse side effects. Here, we use a preclinical model (male Brown Norway X F344 rats aged 12, 18, 24, and 30 months) to describe the outcome of chronic fentanyl administration (1.0 mg/kg/day) on various physiological and behavioral measures. Continuous fentanyl administration resulted in an initial decrease in food consumption, followed by the development of tolerance to this effect over a 4-week period and a subsequent increase in food consumption during withdrawal. This change in food consumption was associated with decreases in body weight (predominantly due to a loss of fat mass) that was maintained through early withdrawal. After one month of withdrawal, only the 12-month old animals had fully regained body weight. Fentanyl administration resulted in a decrease in grip strength and an increase in locomotor activity that did not differ across age groups. There was no effect of fentanyl administration on rotarod performance. These results demonstrate that while there is a delayed recovery of body mass with age, the observed changes in behavioral responses are uniform across ages.

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“…Even after several days of high intake of morphine plus saccharin, the elimination of saccharin from the bottles markedly reduces morphine consumption [ 11 ], thus limiting the translational value of this model. Similarly, rats given morphine adultered with sugar in their drinking water for 21 days do not develop a preference for the morphine-sugar bottle when evaluated against a bottle with only sugar dissolved in water [ 14 ]. Thus, the taste-altering confounding factor must be eliminated before animals that consume morphine could be reliably used for pre-clinical testing of treatments aimed at reducing consumption elicited by morphine itself.…”

Section: Introductionmentioning

confidence: 99%

A Novel Morphine Drinking Model of Opioid Dependence in Rats

Berríos-Cárcamo

Quezada

Santapau

et al. 2022

IJMS

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An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants’ presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.

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Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats

Cited by 8 publications

References 28 publications

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Effects of chronic fentanyl administration on physical performance of aged rats

A Novel Morphine Drinking Model of Opioid Dependence in Rats

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