Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated with morphine and injected with naloxone, in the absence or presence of the antiabstinence agent clonidine

Pinelli, A; Trivulzio, Silvio

doi:10.1016/s1056-8719(97)00050-6

Cited by 30 publications

(35 citation statements)

References 39 publications

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“…Administration of clonidine, an α 2 adrenoceptor agonist, significantly decreased morphine withdrawal symptoms during the first week of withdrawal. This finding is in agreement with previous reports on rhesus monkeys [38] , rodents [47,[50][51][52][53][54][55][56][57][58] , and humans [21,22,59] that clearly demonstrate that clonidine effectively attenuates some opiate withdrawal signs and symptoms. Here, clonidine was able to reduce some, but not all, symptoms of morphine withdrawal (Figure 3).…”

Section: Discussionsupporting

confidence: 93%

“…In contrast, clonidine had no or limited effects on other symptoms such as face flush or grimacing. Previous reports had shown that clonidine only affected a subset of symptoms in monkeys [38] , rats [47] , and humans [21,22,59] . The effects of clonidine on withdrawal symptoms were shortlasting, since the intensity of the morphine withdrawal signs were even higher at the cessation of the clonidine treatment (at week 2), suggesting a rebound phenomenon (Figure 2).…”

Section: Discussionmentioning

confidence: 87%

“…It should be noted that withdrawal in this study was not induced by injections of opiate antagonist, but with the cessation of morphine treatment, a situation that mimics that of human addicts that stop taking drugs. In contrast, many previous investigators have used opioids antagonists, such as naloxone or nalorphine, to induce morphine withdrawal syndrome in monkeys [39] and rodents [40][41][42][43][44][45][46] (see ref 47 for a comparison of studies). The symptoms of withdrawal are often more pronounced when provoked by an injection of an opioid antagonist than provoked by cessation of morphine injections.…”

Section: Discussionmentioning

confidence: 99%

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Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

Chen

Zhai

Yanying

et al. 2007

Acta Pharmacologica Sinica

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Aim: Clonidine is an α 2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus monkeys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic) dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results: Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized responses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may reduce subsequent effects of drugs of abuse after prolonged abstinence.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

Chen

Zhai

Yanying

et al. 2007

Acta Pharmacologica Sinica

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“…Auditory startle amplitudes and startle-induced ultrasonic vocalizations were evaluated in groups of rats undergoing withdrawal from acute or chronic morphine to compare the magnitude of these changes across different states of dependence. The second objective was to determine whether somatic signs, increased urination, and defecation could provide objective quantitative measures of withdrawal from acute dependence as they do withdrawal from chronic dependence (Ho et al, 1979;Pinelli and Trivulzio, 1997). To determine an optimal pretreatment interval for these somatic and behavioral indices of withdrawal, morphine pretreatment times were varied between 2 and 6 h. In a recent drug discrimination study in which rats were trained to discriminate acutely administered morphine followed by naltrexone from saline followed by naltrexone, the maximal discriminative effects occurred at 3 to 4 h (Easterling and Holtzman, 1999).…”

mentioning

confidence: 99%

Changes in Urination/Defecation, Auditory Startle Response, and Startle-Induced Ultrasonic Vocalizations in Rats Undergoing Morphine Withdrawal: Similarities and Differences between Acute and Chronic Dependence

Kalinichev

Holtzman²

2003

J Pharmacol Exp Ther

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In drug-free subjects, a single dose of morphine followed by an opioid antagonist a few hours later results in signs of a withdrawal syndrome, suggesting a state of physical dependence. Increased urination/defecation, altered startle, and ultrasonic vocalizations (USV) are some signs of the withdrawal syndrome in rats chronically dependent on morphine. We investigated whether naltrexone stimulates urination/defecation and alters startle and USV in male rats that were pretreated with only a single dose of morphine and compared these indices to the ones of chronic dependence. Separate groups of rats were pretreated with either a single dose (10 mg/kg) or with a continuous s.c. infusion of morphine via an osmotic pump. Naltrexone (0.01-1.0 mg/kg) was administered 2 to 6 h after the single dose of morphine and on days 7 to 11 of the infusion. Immediately after the naltrexone injection subjects were placed in sound-attenuating boxes to record startle and USV and to collect urine/feces. Subjects chronically exposed to morphine also were tested during spontaneous withdrawal 3 to 24 h after pump removal. Naltrexone increased urination/defecation in subjects pretreated with morphine either chronically or acutely; it increased startle and USV in acutely dependent rats but decreased them in chronically dependent rats. In the latter group, changes in the four variables during spontaneous withdrawal were qualitatively similar to those during precipitated withdrawal but smaller in magnitude. Differences in withdrawal signs between acute and chronic dependence suggest that the neural substrates that mediate those particular components of the withdrawal syndrome are affected differently in the two states of dependence.

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“…Picard et al 12 reported that there is no evidence of the role of opioids in the peripheral analgesia for acute pain; however, it is worth mentioning that they did not evaluate the role of opioid drugs of intra-articular action, being different from the present study which tried to evaluate the antinociceptive effect of exercise and whether it could occur via peripherally and intra-articular opioid, since the naloxone injection followed different dose and via recommended for systemic action [13][14][15] . Sensitization of articular primary afferent nociceptors (peripheral sensitization) and of neurons of the spinal cord (central sensitization) are basic neuronal processes in pain and mechanical hyperalgesia.…”

Section: Local Pressure (G) Local Pressure (G) Discussionmentioning

confidence: 57%

Uso do exercício resistido antagonizado por naloxone como fator de analgesia em sinovite aguda de joelho de ratos Wistar

Bertolini

Rosa

Silva

et al. 2012

Rev Bras Med Esporte

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Analgesia arising from exercising can occur via release of endogenous opioids in the central nervous system and periphery. However, the literature remains controversial about exercise ways and actions in pain. Thus, the aim of this study was to evaluate whether resistance exercise produces changes on the nociception and suffers interference by applying an opioid inhibitor. 18 rats divided into three groups were used: G1 -hyperalgesia on right knee and untreated; G2 -hyperalgesia and treated with jump sin water; G3-hyperalgesia with previous injection of naloxone and subsequent jumps. To produce hyperalgesia,100µl of 5% formalin was injected in the tibio femoral joint space. Pain was assessed using a digital von Frey filament on the right medial tibiofemoral joint. The evaluation periods were: pre-injury (EV1) after 15 minutes (EV2) and 30 minutes (EV3) and one hour (EV4). The applied exercise was jumpingin water and it occurred after EV2. The animal performed 4 sets of 5 jumps, with an interval of 3 minutes and overload of 50% of body weight. In G1, nociceptive increase was observed, with significant decrease and return to initial baseline values in AV4; G2 showed threshold restoration after exercise and return to baseline; G3 reduced thresholds, without restoration or significant increase in them. We concluded that there was analgesia withuse of exercise and that it was altered by blocking beta-endorphin.

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Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated with morphine and injected with naloxone, in the absence or presence of the antiabstinence agent clonidine

Cited by 30 publications

References 39 publications

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

Changes in Urination/Defecation, Auditory Startle Response, and Startle-Induced Ultrasonic Vocalizations in Rats Undergoing Morphine Withdrawal: Similarities and Differences between Acute and Chronic Dependence

Uso do exercício resistido antagonizado por naloxone como fator de analgesia em sinovite aguda de joelho de ratos Wistar

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