Sensitivity to the effects of opioids in rats with free access to exercise wheels: �-opioid tolerance and physical dependence

Smith, Mark A.; Yancey, David L.

doi:10.1007/s00213-003-1471-5

Cited by 83 publications

(65 citation statements)

References 44 publications

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“…This idea have been confirmed by the other studies, which have shown that CSF beta-endorphin levels were increased by voluntary chronic running in rats, and it remained high for the first 2 days after the interruption of running [16,26,27]. All of these evidences show that endogenous opioid levels increase after exercise.…”

Section: Discussionsupporting

confidence: 76%

“…This hypothesis is supported by studies demonstrating that chronic and voluntary wheel running decreases the antinociceptive response to mu-opioid drugs [14,15]. In contrast, chronic and voluntary exercise slightly increases aversive responses to the kappa opioid spiradoline in the CPP task, while simultaneously decreasing the antinociceptive response to spiradoline [16].…”

Section: Introductionmentioning

confidence: 76%

“…the wheel running must activate at least some of the same systems that are activated by morphine and other opiates [13]. It has been suggested that during chronic, long-term exercise the sensitivity to the effects of morphine and other mu opioids decreases [16].…”

Section: Discussionmentioning

confidence: 99%

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Treadmill exercise reduces self-administration of morphine in male rats

et al. 2009

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 76%

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Treadmill exercise reduces self-administration of morphine in male rats

et al. 2009

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“…As reported previously (Smith and Yancey, 2003;Smith and Lyle, 2006), exercise output gradually increased over the first 3 weeks of wheel exposure before leveling out until behavioral testing commenced. Exercise output decreased in all rats by approximately 50% with the acquisition of self-administration and then remained consistent until the end of behavioral testing.…”

Section: Discussionsupporting

confidence: 56%

Aerobic exercise decreases the positive-reinforcing effects of cocaine

Smith

Schmidt

Iordanou

et al. 2008

Drug and Alcohol Dependence

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138

146

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Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixedratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3 mg/kg/infusion) and high (1.0 mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

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“…Allowing rats free access to a running wheel for 3 weeks resulted in lower tail flick latencies compared with nonrunning rats. 9,21,24,25,45,46 The active rats showed a lower analgesic response to opioid analgesics administered peripherally, systemically, or into the periaqueductal gray in the midbrain. 24,25 These data suggest that running wheel activity increases release of endogenous opioid peptides.…”

Section: Exercise Training and Analgesiamentioning

confidence: 99%

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

Yokoyama

Lisi

Moore

et al. 2007

The Journal of Pain

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Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 µL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were run for 2 h/day for 2 days prior to the first injection and 2 h/day for 2 days prior to the second injection. Muscle lactate, pCO 2 , pO 2 , creatinine kinase, phosphate, and histology were examined after the fatigue task and compared to a control group. Grip force was significantly decreased after 2 h of running indicating fatigue. The fatigue task did not induce muscle damage as there was no difference in muscle lactate, pCO 2 , pO 2 , creatinine kinase, phosphate, or histology. The fatigue task altered the dose-response relationship to intramuscular acidic saline injections. Mechanical hyperalgesia was observed in both fatigue and control groups after intramuscular injection of pH 4.0, but only the fatigue group after injection of pH 5. Neither the fatigue nor the control group developed hyperalgesia in response to intramuscular injection of pH 6 or pH 7.2. In conclusion, fatigue modified the susceptibility of mice to acid injection of pH 5.0 to result in mechanical hyperalgesia after 2 injections of pH 5.0. The fatigue task did not produce measurable changes in the muscle tissue suggesting a central mechanism mediating the enhancement of hyperalgesia.Perspective-These data therefore show that muscle fatigue can enhance the likelihood that one develops pain to a mild insult. Clinically, this could relate to the development of pain from such conditions as repetitive strain injury, and may relate to the interrelationship between chronic pain and fatigue. KeywordsFatigue; exercise; acid; protons; low-pH saline Pain arising from musculoskeletal disorders is a major clinical problem globally, 58 and fibromyalgia affects 2% of population in the United States. 57 As high as 76% of people with chronic widespread musculoskeletal pain conditions, such as fibromyalgia and arthritis, also report fatigue. 26 Conversely, as high as 94% of people with chronic fatigue syndrome report musculoskeletal pain and approximately half of the population has chronic widespread musculoskeletal pain. 56,60 Pain is increased during and after exercise in people with fibromyalgia and chronic fatigue syndrome. 20,48,54,55 Similarly, muscle fatigue is increased in people with chronic fatigue syndrome. 3,10,23 To assess mechanisms of chronic widespread pain, we developed an animal model that mimics the clinical symptoms. Two injections of acidic saline (pH 4.0), 5 days apart, into 1 muscle results in bilateral long-lasting hyperalgesia of the paw, 41 muscle,59 and the viscera28 without muscle tissue damage.41 The intramuscular pH decreases to a p...

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Sensitivity to the effects of opioids in rats with free access to exercise wheels: �-opioid tolerance and physical dependence

Abstract: These data suggest that chronic exercise leads to the development of mu-opioid tolerance and physical dependence, and that these effects are similar to those produced by chronic opioid administration.

Cited by 83 publications

References 44 publications

Treadmill exercise reduces self-administration of morphine in male rats

Treadmill exercise reduces self-administration of morphine in male rats

Aerobic exercise decreases the positive-reinforcing effects of cocaine

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

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