Morphine Analgesia and Cerebral Opiate Receptors: A Developmental Study

Auguy-Valette, A.; Cros, J.; Gouardères, Christine; Gout, Robert; Pontonnier, G

doi:10.1111/j.1476-5381.1978.tb09761.x

Cited by 77 publications

(17 citation statements)

References 11 publications

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“…Nociceptive threshold testing in rat pups has shown that the analgesic potency of systemic morphine to mechanical stimulation is significantly greater in the neonate and declines with post‐natal age (Nandi et al, 2004). However, other studies showed that the analgesic potency of morphine in rat pups increases with maturation, due to (a) the proliferation of opiate receptors (Auguy‐Valette et al, 1978; Zhang and Pasternak, 1981) and (b) the maturation of supra‐spinal descending inhibition, which becomes functional at 3 weeks post‐natal (Beland and Fitzgerald, 2001). The changing morphine sensitivity in the post‐natal period may be part of a general reorganization in the structure and function of primary afferent synapses, neurotransmitter/receptor expression and function and excitatory and inhibitory modulation from higher brain centers (Fitzgerald and Beggs, 2001; Fitzgerald and Howard, 2003; Pattinson and Fitzgerald, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Nociceptive threshold testing in rat pups has shown that the analgesic potency of systemic morphine to mechanical stimulation is significantly greater in the neonate and declines with post‐natal age (for review see Nandi and Fitzgerald, 2005). In contrast, there are studies that demonstrate that the analgesic potency of morphine in rat pups increases with maturation, due to (a) the proliferation of opiate receptors (Auguy‐Valette et al, 1978; Zhang and Pasternak, 1981) and (b) the maturation of supra‐spinal descending inhibition, which becomes functional at 3 weeks post‐natal (Nandi and Fitzgerald, 2005). Although descending inhibitory mechanisms are not still completely formed until the third week of life (Nandi and Fitzgerald, 2005), morphine and other opiate agonists are effective analgesics during the early neonatal period due to the presence of spinal opiate receptors at birth (Rahman and Dickenson, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Long‐term effect of morphine administration in young rats on the analgesic opioid response in adult life

Rozisky

Dantas

Adachi

et al. 2008

Intl J of Devlp Neuroscience

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Neonates, infants and children are often exposed to pain from invasive procedures during intensive care and during the post-operative period. Opioid anesthesia and post-operative opioid analgesia have been used in infants and result in clinical benefits. The objectives of this study were to verify the effect of repeated 5 microg morphine administration (subcutaneous), once a day for 7 days in 8-day-old rats, at P8 until P14. To verify the long-term effect of morphine, the animals were submitted to a second exposure of 5mg/kg (intraperitoneal) of morphine at P80 until P86. Animals that received morphine for 7 days, at P14 did not develop tolerance, however at P80, rats demonstrated greater morphine analgesia. At P86, after 7 days of morphine administration, animals showed classical tolerance. These findings may have important implications for the human neonate, suggesting a possible explanation for the differences in the requirements of morphine observed in the youngest patients.

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Section: Discussionmentioning

confidence: 99%

“…Nociceptive threshold testing in rat pups has shown that the analgesic potency of systemic morphine to mechanical stimulation is significantly greater in the neonate and declines with post‐natal age (for review see Nandi and Fitzgerald, 2005). In contrast, there are studies that demonstrate that the analgesic potency of morphine in rat pups increases with maturation, due to (a) the proliferation of opiate receptors (Auguy‐Valette et al, 1978; Zhang and Pasternak, 1981) and (b) the maturation of supra‐spinal descending inhibition, which becomes functional at 3 weeks post‐natal (Nandi and Fitzgerald, 2005). Although descending inhibitory mechanisms are not still completely formed until the third week of life (Nandi and Fitzgerald, 2005), morphine and other opiate agonists are effective analgesics during the early neonatal period due to the presence of spinal opiate receptors at birth (Rahman and Dickenson, 1999).…”

Section: Introductionmentioning

confidence: 99%

Long‐term effect of morphine administration in young rats on the analgesic opioid response in adult life

Rozisky

Dantas

Adachi

et al. 2008

Intl J of Devlp Neuroscience

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“…Moreover, the responses to naloxone, like those in the adult, appeared to be mediated by a catecholaminergic mechanism for they were blocked readily by alfuzosin. It also seems unlikely that discordance between the Gn RH responses to opioid recep tor blockade in the immature rat in vitro and in vivo reflects the inability of the drug to reach the receptors, for naloxone readily crosses the blood-brain barrier and has been shown to influence other aspects of brain function in young rats of a similar age [48]. A more plausible explanation may be that the immature male rat is more sensitive to the inhibitory effects of stress on gonadotrophin secretion, a concept which is supported by our observation that the reduction in serum LH elicited by the injec tion procedure is overcome readily by naloxone.…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro Studies on the Opioidergic Control of the Secretion of Gonadotrophin-Releasing Hormone and Luteinizing Hormone in Sexually Immature and Adult Male Rats

1991

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In vivo and in vitro methods have been used to compare the effects of opioid receptor blockade on the functional activity of the hypothalamo-pituitary-gonadal axis in adult (200 g) and sexually immature (50 g) male rats. In the adult, a single injection of the µ-receptor antagonist, naloxone (500 µg/100 g body weight, s.c), produced hypersecretions of luteinizing hormone (LH) and testosterone. Maximal serum concentrations of the two hormones were attained within 20 and 60 min respectively. In contrast, neither ICI 174864 (100 µg/100 g body weight, s.c.) nor MR2266 (150 µg/100 g body weight, s.c), which block δ- and ĸ-receptors respectively, stimulated pituitary-gonadal activity; indeed, like the saline vehicle, both tended to depress the serum LH concentration. The injection procedure was sufficient to activate the hypothalamo-pituitary-adrenal axis and, thus, the vehicle-treated controls exhibited significant increases in the plasma adrenocorticotrophin and serum corticosterone concentrations. These effects were enhanced by naloxone (500 µg/100 g body weight, s.c.) and by the ĸ-opioid receptor (MR2266, 150 µg/100 g body weight, s.c.) but not by the δ-opioid receptor antagonist (ICI 174864, 30–100 µg/100 g body weight, s.c). The increases in serum corticosterone and LH concentration induced by naloxone in adult rats were not apparent in the sexually immature (50 g) animals. To the contrary, in the young rats naloxone (250 and 500 µg/100 µg body weight, s.c.) attenuated, in a dose-dependent manner, the pronounced hypersecretion of corticosterone induced by the vehicle injection. The higher dose of the antagonist (500 µg/100 g body weight, s.c.) also overcame the significant reductions in serum LH evident 20 (p < 0.05) and 40 (p < 0.01) min after the saline injection but the lower dose (250 µg/100 g body weight, s.c.) was ineffective in this respect. In vitro, hypothalami from both adult and sexually immature rats responded to the addition of naloxone (10^–8–10^–6M) to the incubation medium with significant (p < 0.01) concentration-dependent increases in the release of gonadotrophin-releasing hormone (GnRH). In contrast, ICI 174864 (10"⁷–10^–6M) and MR2266 (10^-7–10^-6M) had little effect on the secretion of the releasing hormone by hypothalami from rats of either group although, at the highest concentration tested, MR2266 (10^–6M) precipitated a small increase in GnRH release from hypothalami from adult rats. The secretory responses of hypothalami from adult and prepubertal rats to naloxone were inhibited by the inclusion in the medium of the αi-adrenoceptor antagonist alfuzosin (10-⁶M) which, in the absence of naloxone, had no discernible effects on GnRH release. Receptor binding studies indicated that both the density and affinity of naloxone-sensitive opioid binding sites within the hypothalamus were similar in adult and sexually immature rats. The results demonstrate marked differences between the neuroendocrine responses of adul...

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“…Evidence demonstrating gradual development of opiate receptor den sity in the brain during the postnatal growth has been presented by Coyle and Pert [8], Development of opiate receptors in rat brain during ontogen esis was studied using in vitro 3H-naloxone binding to crude mitochondrial fraction [2]. Increase in binding during the development (5,10,15,20,30, and 60 days old) was attributed to an increase in the maximal number of binding sites (Bmax), the affinity values (KD) remained unchanged.…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Alterations in the Accumulation of /-Methadone in the Brain Synaptosomes and Other Subcellular Fractions

Sha¹,

Sha²

1984

Dev Pharmacol Ther

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Albino Sprague-Dawley rats (1, 8, 12 and 20 days old) were injected intra- peritoneally with l-[^3H-l]-methadone (5 mg/kg containing 50 μCi/kg), and sacrificed at 15 min, 1 h and 3 h. Whole brain was homogenized in 0.32 M sucrose-Tris buffer and the homogenates were subjected to differential centrifugation to separate nuclei, mitochondria, microsomes, soluble cytosol, myelin, membrane and synaptosomes. Methadone levels in each fraction were examined. The methadone contents in the whole brain (sum of all fractions) of 1- and 8-day-old rats were significantly higher relative to those of 12- and 20-day-old rats at all time intervals. The most striking finding in this study was that during development, the percentage of methadone content in the synaptosomal fraction progressively increased relative to other subcellular fractions; interestingly, there was an associated decrease in the percent levels in the soluble cytosol suggesting a shift of methadone from cytosol to synaptosomes. These alterations in brain synaptosomal accumulation of methadone could result from the progressive increase in the affinity of methadone for synaptosomes as these particles become enriched in the protein and lipid contents and possibly increase in opiate receptor density during the neuronal maturation and the synap- togenesis of the developing brain.

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Morphine Analgesia and Cerebral Opiate Receptors: A Developmental Study

Cited by 77 publications

References 11 publications

Long‐term effect of morphine administration in young rats on the analgesic opioid response in adult life

Long‐term effect of morphine administration in young rats on the analgesic opioid response in adult life

In vivo and in vitro Studies on the Opioidergic Control of the Secretion of Gonadotrophin-Releasing Hormone and Luteinizing Hormone in Sexually Immature and Adult Male Rats

Age-Dependent Alterations in the Accumulation of /-Methadone in the Brain Synaptosomes and Other Subcellular Fractions

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