Opiate withdrawal in the neonatal rat: relationship to duration of treatment and naloxone dose

Ceger, Patricia; Kuhn, Cynthia M.

doi:10.1007/s002130000413

Cited by 29 publications

(21 citation statements)

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“…Thus, as in the adult rat, acute opiate withdrawal exists in the infant rat. Our results are consistent with the only other available report on acute opiate withdrawal in the infant rat (Ceger and Kuhn 2000) and we extended the findings of that study by demonstrating that, in addition to withdrawal behaviors, molecular indices such as c-fos mRNA expressions are also increased.…”

Section: Acute Opiate Withdrawal Exists In Infantsupporting

confidence: 92%

“…Thus, the pharmacological effects of NMDA antagonism in the infant may not necessarily be comparable to those in the adult. In fact, the acute or chronic administration of NMDA receptor antagonists is ineffective in suppressing the expression of the behavioral signs of withdrawal from chronic morphine treatment followed by naltrexone challenge, in the 4 to 7-day-old rat (Bell and Beglan 1995; Barr 2000, 2001), which is in contrast to reports in the adult (Trujillo and Akil 1991a).Although several laboratories, including ours, have examined the behavioral, biochemical and pharmacological aspects of opiate withdrawal induced by chronic opiate administration in the infant animals Barr 1995, 2000;Windh et al 1995;Ceger and Kuhn 2000; Barr 2000, 2001), little is known about the acute morphine withdrawal syndrome in the infant animal model (Ceger and Kuhn 2000). Thus, the present study investigated the behavioral and biochemical parameters of acute morphine withdrawal in the 7-day-old rat.…”

mentioning

confidence: 76%

“…Although several laboratories, including ours, have examined the behavioral, biochemical and pharmacological aspects of opiate withdrawal induced by chronic opiate administration in the infant animals Barr 1995, 2000;Windh et al 1995;Ceger and Kuhn 2000; Barr 2000, 2001), little is known about the acute morphine withdrawal syndrome in the infant animal model (Ceger and Kuhn 2000). Thus, the present study investigated the behavioral and biochemical parameters of acute morphine withdrawal in the 7-day-old rat.…”

mentioning

confidence: 91%

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Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

Jones

Zhu

Jenab

et al. 2002

Neuropsychopharmacology

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The present study examined the ability of LY235959, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, to attenuate behaviors and c-fos mRNA expression associated with acute morphine withdrawal in the infant rat. Rat pups were given a single dose of morphine (10.0 mg/kg, s.c.) or saline. Two hours later, pups were removed from the dam and injected with either LY235959 (10.0 mg/kg, s.c.) In humans, exposure to opiates for either medical or nonmedical reasons leads to dramatic behavioral and neural changes resulting in physical dependence (Trujillo and Akil 1991b). Although physical dependence is classically thought to develop after chronic exposure to opiates (chronic opiate dependence), the adaptational changes underlying physical dependence begin with the first exposure to an opiate (Heishman et al. 1989a,b;Kirby et al. 1990). Thus, acute opiate withdrawal refers to the withdrawal syndrome precipitated by administration of an opioid antagonist after either a single dose or a short-term infusion of opioid agonist (Martin and Eades 1964;Bickel et al. 1988).Despite decades of research, our understanding of the mechanisms underlying opiate physical dependence and withdrawal is still very limited (Mayer et al. 1999;Trujillo 1999) and multiple mechanisms may operate in these processes (Thorat et al. 1994). There is increasing evidence indicating that N-methyl-D-aspartate (NMDA) receptor antagonists inhibit the development of mu receptor mediated opiate dependence in the adult NO . 3 rodent, and that the NMDA receptor and its second messenger systems play pivotal roles in opiate tolerance, dependence and withdrawal (Trujillo and Akil 1991a;Inturrisi 1997;Mao 1999;Mayer et al. 1999).It is not known whether these mechanisms in adults apply to infants. On the one hand, opiate dependence can be established in fetuses or infant rat pups if the dams are exposed to opiates during their pregnancy or the pups are treated directly with opiates Barr 1995, 2000;Windh et al. 1995;Barr et al. 1998). On the other hand, the neonatal CNS is both structurally and functionally different from that of the adult, and significant changes in opioid actions occur both prenatally and postnatally (Barr 1992(Barr , 1993Fitzgerald 1995;Marsh et al. 1997;Fitzgerald and Jennings 1999). More importantly, the NMDA receptor, which is believed to play a crucial role in the establishment of opiate dependence, undergoes qualitative and quantitative changes during development (Kalb et al. 1992;Hori and Kanda 1994;Kalb and Fox 1997). These include significant developmental alterations both in the density of the receptor (Tremblay et al. 1988;Morin et al. 1989;Represa et al. 1989), the sensitivity of the receptor complex to magnesium Bowe and Nadler 1990;Morrisett et al. 1990), and the rise and decay times of the NMDA receptor-mediated excitatory post-synaptic currents (EPSCs) (Akaike and Rhee 1997;Bardoni et al. 1998). Recently, due to the advancement in cloning technology and gene knockout technology, the molecular structure of the...

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Section: Acute Opiate Withdrawal Exists In Infantsupporting

confidence: 92%

mentioning

confidence: 76%

mentioning

confidence: 91%

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Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

Jones

Zhu

Jenab

et al. 2002

Neuropsychopharmacology

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“…Behaviors during the last 6 out of 8 minutes of video were analyzed by an experimenter blinded to animal treatment. During the assessment period, behaviors were recorded at 15 second intervals on a checklist of age-specific behaviors associated with naloxone precipitated withdrawal following acute or chronic opioid administration in neonatal rats (Jones and Barr, 1995, Windh et al, 1995, Ceger and Kuhn, 2000. The number of occurrences of each behavior was summed across the 6 minute observation period.…”

Section: Spontaneous Withdrawal Behaviors Infant Ratsmentioning

confidence: 99%

“…The number of occurrences of each behavior was summed across the 6 minute observation period. Age specific withdrawal behaviors which included head movements, paw movements, rolling, wall climbing, walking, and quiet were scored (Jones and Barr, 1995, Windh et al, 1995, Ceger and Kuhn, 2000. A quiet score was given when the animal was not moving.…”

Section: Spontaneous Withdrawal Behaviors Infant Ratsmentioning

confidence: 99%

Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats

Zissen,

Zhang,

McKelvy

et al. 2007

Neuroscience

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Our laboratory has previously characterized age-dependent changes in nociception upon acute morphine withdrawal. This study characterizes changes in mechanical and thermal nociception following acute, intermittent, or continuous morphine administration in infant (postnatal day 5-8) and young (postnatal day 19-21). Morphine was given as a single acute administration (AM), intermittently twice a day for 3 days (IM), or continuously for 72 hours via a subcutaneous pump implanted (CM). AM did not produce long-term changes in mechanical or thermal nociception in either infant or young rats. CM produced changes in mechanical nociception that included the development of tolerance, opioid-induced mechanical allodynia and withdrawal-associated mechanical allodynia in young rats, but only tolerance and a prolonged withdrawal-associated mechanical allodynia in infant rats. IM produced withdrawal-associated mechanical allodynia in both infant and young rats. Measuring paw withdrawal responses to thermal stimuli, infant and young rats showed tolerance without opioid-induced thermal hyperalgesia or withdrawal-associated thermal hyperalgesia following CM. In contrast to CM, withdrawal-associated thermal hyperalgesia was seen in both ages following IM. In conclusion, CM versus IM differentially modified mechanical and thermal nociception, suggesting that opioid-dependent thermal hyperalgesia and mechanical allodynia can be dissociated from each other in infant and young rats. Furthermore, tolerance, opioidinduced hypersensitivity, and withdrawal-associated hypersensitivity are age-specific and may be mediated by distinct mechanisms.Keywords morphine withdrawal; spinal cord; allodynia; hyperalgesia; neonatal rat It has long been recognized that morphine exerts two paradoxical actions on the adult nervous system: the inhibition of pain processing manifested as analgesia and the facilitation of nociceptive sensitivity manifested as allodynia and hyperalgesia (Bederson et al., 1990, Kim et al., 1990, Kaplan and Fields, 1991. This facilitation of nociceptive sensitivity can be observed in as little as 20 min post-morphine administration by precipitating withdrawal with Corresponding Author: Sarah M. Sweitzer, PhD, Department of Pharmacology, Physiology, Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, Phone: (803) Fax: (803) 733-1523 Email: sweitzer@med.sc.edu. Section Editor: Dr. Donna Hammond Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 January 5. (Bede...

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Prenatal Exposure to Opioids

Schrott

2014

Contemporary Clinical Neuroscience

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Opiate withdrawal in the neonatal rat: relationship to duration of treatment and naloxone dose

Abstract: These results demonstrate that the intensity of neonatal opiate withdrawal is related to the duration and intensity of treatment. The profile of observed withdrawal behaviors may reflect the involvement of the noradrenergic system.

Cited by 29 publications

References 27 publications

Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats

Prenatal Exposure to Opioids

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