Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence

Thornton, Suzanne R.; Smith, Forrest L.

doi:10.1016/s0014-2999(98)00783-3

Cited by 32 publications

(32 citation statements)

References 36 publications

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“…Alzet osmotic minipumps were surgically implanted as previously described in detail (26,27). Briefly, P14 rat pups were anesthetized with 0.5% methoxyflurane (minimal alveolar concentration ϭ 0.23%) for implantation of Alzet 1003D osmotic minipumps (Alza Corp, Palo Alto, CA, U.S.A.) that deliver at a rate of 1 L/h.…”

Section: Methodsmentioning

confidence: 99%

“…Fentanyl citrate concentrations were adjusted to deliver at a rate of 60 g/kg/h. This infusion rate was based on a series of implantation trials that led to the initial characterization of fentanyl tolerance and dependence in P17 rat pups (27).…”

Section: Methodsmentioning

confidence: 99%

“…This laboratory has developed and characterized a neonatal and infant rat model of fentanyl tolerance and physical dependence (26,27). Dependence has been demonstrated with naloxone-precipitated withdrawal.…”

mentioning

confidence: 99%

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Buprenorphine Substitution Ameliorates Spontaneous Withdrawal in Fentanyl-Dependent Rat Pups

Lohmann

Smith

2001

Pediatr Res

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Buprenorphine Substitution Ameliorates Spontaneous Withdrawal in Fentanyl-Dependent Rat Pups

Lohmann

Smith

2001

Pediatr Res

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“…In adult rats, both μ and δ receptors are functional, and it has been unknown whether high doses of morphine can elicit antinociception through δ receptors. Recently, it was demonstrated that high doses of morphine elicit antinociception in μ knockout mice by stimulating κ, but not δ, opioid receptors [37] Finally, a previous study demonstrated that fentanyl tolerant infant rats were desensitized to morphine as P50 juvenile and P90 adult rats [32]. In addition, in utero exposure to morphine led to a decrease in morphine's antinociceptive potency in infant and juvenile rats [14].…”

Section: Behavioral Expression Of Morphine Tolerance In P17 Ratsmentioning

confidence: 99%

“…Alzet® osmotic minipumps were surgically implanted as previously described [32]. P14 rat pups, weighing 30 g, were anesthetized with isoflurane USP (Henry Schein, Inc. Melville, NY, U.S.A.) for implantation of Alzet 1003D osmotic minipumps with a delivery rate of 1μL/h.…”

Section: Surgical Implantation Of Osmotic Minipumpsmentioning

confidence: 99%

Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine-tolerant infant rats

2007

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We have previously noted that the antinociceptive efficacy of morphine was significantly decreased in rat pups chronically infused with morphine from implanted osmotic minipumps. In this study, morphine was fully efficacious (i.e., 100% maximum possible effect, %MPE) in the 52 ºC tail-immersion test after a 72-h infusion from implanted saline-filled osmotic minipumps. However, administration of up to 1000 mg/kg s.c. morphine failed to elicit greater than a 27% MPE in rats infused with morphine at 2 mg/kg/h. Morphine was more efficacious when the water bath temperature was decreased to 49 ºC. Experiments were conducted to determine the mechanisms whereby chronic morphine administration leads to a decrease in antinociceptive efficacy. The kappa-opioid antagonist nor-binalorphimine completely blocked the antinociceptive effects of morphine in morphine-infused rat pups. The kappa agonist U50,488 elicited antinociception however, the requirement to use higher doses in morphine-than saline-infused rats indicates that kappa cross-tolerance was present. Thus, in tolerant rats the antinociceptive effects of high doses of morphine appear to be mediated through kappa-opioid receptors. The deltaopioid antagonist naltrindole was inactive in both treatment groups. DAMGO-stimulated [ 35 S]GTPγS and [ 3 H]naloxone binding reveal that the anatomical distribution of the mu-opioid receptor was consistent with that of the adult rat brain. In adult rats, the mu-opioid receptor is desensitized during morphine tolerance. However, desensitization was not evident in P17 rats based on the lack of significant decreases in [ 35 S]GTPγS binding. Furthermore, [ 3 H]naloxone binding indicated a lack of mu receptor downregulation in morphine-tolerant rat pups.

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Morphine exposure induces age‐dependent alterations in pentylenetetrazole‐induced epileptic behaviors in prepubertal rats

Gholami

Saboory

2012

Developmental Psychobiology

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Opioids show both pro- and anti-epileptogenic effects in different experimental models of epilepsy. In the present study, the pentylentetrazole (PTZ)-induced seizure model was used to test the hypothesis that neonatal morphine administration affects seizure susceptibility in prepubertal rats. Female rats were subcutaneously injected with either morphine or saline on postnatal days 8-14 (P8-P14). To verify the long-term effect of morphine (or saline), the animals were treated second time with morphine (21 mg/kg; or saline) on either P25 or P32. Morphine administration decreased latency of myoclonic jerks and time to onset and increased tonic-clonic seizure rate at P25, but these findings were inversed at P32. Results showed a significant age difference in seizure behaviors between P25 and P32 animals. Blood corticosterone (COS) levels were significantly higher in P32 rats than in P25 rats. These findings show that neonatal morphine exposure plays an important role in increasing seizure vulnerability in P25 prepubertal rats but not in P32 rats. We conclude that early exposure to chronic morphine in infant rats might change their susceptibility to PTZ-induced seizure in an age-dependent manner.

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Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence

Cited by 32 publications

References 36 publications

Buprenorphine Substitution Ameliorates Spontaneous Withdrawal in Fentanyl-Dependent Rat Pups

Buprenorphine Substitution Ameliorates Spontaneous Withdrawal in Fentanyl-Dependent Rat Pups

Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine-tolerant infant rats

Morphine exposure induces age‐dependent alterations in pentylenetetrazole‐induced epileptic behaviors in prepubertal rats

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