Quantitative Properties of Plasma Corticosterone Elevation Induced by Naloxone-Precipitated Withdrawal in Morphine-Dependent Rats

Kishioka, Shiroh; Nishida, Shigeru; Fukunaga, Yuko; Yamamoto, Hiroyuki

doi:10.1254/jjp.66.257

Cited by 22 publications

(9 citation statements)

References 16 publications

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“…If the severity of naloxone-precipitated withdrawal is related to the rate of morphine removal, a correlation of plasma morphine concentration with the naloxone-precipitated withdrawal would be expected. On the other hand, it has been reported that naloxoneprecipitated body weight loss (4) and plasma corticosterone (PCS) increase (5,6) are quantitative indicators of morphine withdrawal, and we have shown that the intensities of both signs were related to the dose of naloxone and the duration of morphine treatment, indicating that the magnitude of the body weight loss and the PCS increase reflect the degree of morphine dependence (7).…”

mentioning

confidence: 60%

No Relation of Plasma Morphine Level to the Severity of Naloxone-Induced Withdrawal in Acute Morphine-Dependent Rats

Kishioka¹,

Inoue²,

Nishida³

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-Plasma morphine concentration and naloxone-precipitated withdrawal body weight loss and plasma corticosterone (PCS) increase were determined at 12, 18 and 24 hr after i.v. infusion of morphine at a constant rate of 10 mg/kg/hr for 4 hr in Sprague-Dawley rats. Plasma morphine concentration declined 98.0% within 12 hr and further declined 58.8% during 12-24 hr after morphine infusion. There was a significant difference between plasma morphine concentrations at 12 and 24 hr after the morphine infusion. Naloxone (0.5 and 2.0 mg/kg)-precipitated withdrawal, but not spontaneous withdrawal, was elicited at 12-24 hr after the morphine infusion, and the severity of withdrawal precipitated by 2.0 mg/kg naloxone was the same at 12-24 hr after the morphine infusion. Furthermore, there was no significant correlation between plasma morphine concentration and body weight loss or PCS increase. The results suggest that a constant degree of morphine dependence is sustained during 12-24 hr after the morphine infusion and the severity of naloxone-precipitated withdrawal is not related to the plasma morphine concentration at the time of naloxone injection, that is, the rate of morphine removal from its receptor sites.Keywords: Intravenous morphine infusion, Plasma morphine concentration, Naloxone-withdrawal, Body weight loss, Plasma corticosterone increase Physical dependence on morphine is evidenced by the withdrawal syndromes that follow the discontinuation of morphine exposure (spontaneous withdrawal) or the treatment with an opioid antagonist (antagonist-precipitated withdrawal) in laboratory animals (1); the severity of the syndrome is thought to reflect the degree of physical dependence. Morphine withdrawal must be initiated by the removal of morphine from opioid receptors.Yoburn et al. (2) demonstrated that the time course of morphine withdrawal was inversely related to the elimination rate of plasma morphine and that body weight loss correlated with plasma morphine levels just before withdrawal in rats implanted with morphine pellets. Furthermore, Domino et al. (3) showed that the negative relationship between the plasma morphine concentration and the severity of withdrawal could be quantified in a simple logarithmic equation in morphine-dependent monkeys. The plasma morphine level has been thought to correlate with the morphine concentration in the vicinity of their binding sites and the amount of morphine bound to opioid receptors. These findings, then, suggest that the severity of morphine withdrawal is related to the rate of removal of morphine from the opioid receptors in spontaneous morphine withdrawal.Opioid antagonist, naloxone-precipitated morphine withdrawal is thought to be initiated through an immediate replacement of morphine by naloxone at their binding sites. Thus the rate of morphine removal from the receptor sites after sufficient naloxone may depend on the morphine concentration in the receptor sites at the time of naloxone injection. If the severity of naloxone-precipitated withdrawal is related ...

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confidence: 60%

No Relation of Plasma Morphine Level to the Severity of Naloxone-Induced Withdrawal in Acute Morphine-Dependent Rats

Kishioka¹,

Inoue²,

Nishida³

et al. 1995

Japanese Journal of Pharmacology

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“…The withdrawal signs of NIC closely resemble the commonly observed withdrawal signs of opioids (44). It has been reported that an increase in CORT levels is one of the signs of morphine withdrawal and that the magnitude of the increase is an effective, objective, and quantitative indicator of spontaneous and opioid-receptor antagonist-precipitated morphine withdrawal in rodents (45,46). The CORT increase elicited by morphine withdrawal is caused by the activation of A2 adrenergic cells in the nucleus of the solitary tract (47), which is mechanistically similar to the NIC-induced activation of the HPA axis (35).…”

Section: Physical Dependencementioning

confidence: 99%

Nicotine Effects and the Endogenous Opioid System

et al. 2014

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Abstract. Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionineenkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by a4b2 and a7 nAChRs, while NIC-induced HPA axis activation is mediated by a4b2, not a7, suggesting that the effects of NIC on the endogenous opioid system are mediated by a7, not a4b2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an a7 antagonist, but not an a4b2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the a7 nAChR.

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“…The increases in SCS level precipitated by morphine withdrawal have been reported already in rodents (1,4). However, it has not been reported that the degree of SCS elevation could be a quantitative index as magnitude of morphine withdrawal in mice.…”

Section: Discussionmentioning

confidence: 58%

“…However, there were not any more quantitative and objective indexes for morphine withdrawal than body weight loss. We have reported the elevated concentration of plasma corticosterone (CS) for useful index as physical dependence on morphine in rats, which is induced putatively by activation of hypothalamopituitary-adrenal (HPA) axis (1). Therefore an increment of CS level in blood induced by naloxone (μ-opiate receptor antagonist) in rodents repeatedly treated with morphine could be an objective index as physical dependence.…”

Section: Introductionmentioning

confidence: 99%

Availability of serum corticosterone level for quantitative evaluation of morphine withdrawal in mice

Ueno

Maeda

Kiguchi

et al. 2011

DD&T

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Physical dependence on morphine is evidenced by the withdrawal syndromes, including body weight loss, which are induced by the discontinuation of morphine exposure or by the treatment with naloxone, an opioid receptor antagonist. The present study was designed to examine whether the elevation of serum corticosterone (SCS) level induced by naloxoneprecipitated morphine withdrawal was a useful index to quantify the physical dependence on morphine in mice, which was compared with body weight loss induced by naloxone-precipitated morphine withdrawal. The SCS level was dependent on the dosage and the number of dosing of morphine and challenging dosage of naloxone. Intraplantar injection of formalin, potentially producing inflammatory pain, inhibited both body weight loss and SCS increase induced by naloxone challenge in mice receiving repeated exposure of morphine, indicating that formalin-induced pain attenuated the development of physical dependence on morphine. The magnitude of body weight loss in morphine withdrawal was significantly correlated with the magnitude of naloxone challenge-induced SCS increase. These results suggest that the naloxoneinduced increase in SCS level is a quantitative index of the magnitude of physical dependence on morphine in mice.

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Quantitative Properties of Plasma Corticosterone Elevation Induced by Naloxone-Precipitated Withdrawal in Morphine-Dependent Rats

Cited by 22 publications

References 16 publications

No Relation of Plasma Morphine Level to the Severity of Naloxone-Induced Withdrawal in Acute Morphine-Dependent Rats

No Relation of Plasma Morphine Level to the Severity of Naloxone-Induced Withdrawal in Acute Morphine-Dependent Rats

Nicotine Effects and the Endogenous Opioid System

Availability of serum corticosterone level for quantitative evaluation of morphine withdrawal in mice

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