Inhibition of growth in young mice treated with d,l-methadone

Smith, Alvy Ray; Hui, Ferdinand W.; Crofford, Marsha

doi:10.1016/0014-2999(77)90036-x

Cited by 41 publications

(8 citation statements)

References 5 publications

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“…Clinical observations of infants and children exposed in early life to opiates such as heroin and methadone reveal a retardation in somatic and neurobiological development (4). Similar perturbations in growth have been reported in laboratory animals subjected to opioids perinatally (1)(2)(3)5) and in cells in culture treated with exogenous and endogenous opioids (6). This interference in growth is stereospecific and is blocked by coadministration of narcotic antagonists (2,5), with the locus of opioid action postulated to reside at the opiate receptor (2,7).…”

Section: Developmentsupporting

confidence: 69%

“…Similar perturbations in growth have been reported in laboratory animals subjected to opioids perinatally (1)(2)(3)5) and in cells in culture treated with exogenous and endogenous opioids (6). This interference in growth is stereospecific and is blocked by coadministration of narcotic antagonists (2,5), with the locus of opioid action postulated to reside at the opiate receptor (2,7). We administered naltrexone, a potent narcotic antagonist, to infant rats at a dosage that continuously blocks the opiate receptor from interaction with endogenous opioid peptides.…”

Section: Developmentsupporting

confidence: 69%

“…Opioid compounds, in addition to having analgesic and behavioral effects, are known to alter cell function and growth, particularly in developing neural systems (1)(2)(3). Clinical observations of infants and children exposed in early life to opiates such as heroin and methadone reveal a retardation in somatic and neurobiological development (4).…”

Section: Developmentmentioning

confidence: 99%

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Increased Brain Size and Cellular Content in Infant Rats Treated with an Opiate Antagonist

Zagon

McLaughlin

1983

Science

206

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From birth to day 21, rat offspring received daily injections of naltrexone at a dosage that blocked morphine-induced analgesia 24 hours a day. At 21 days, body, brain, and cerebellar weights of naltrexone-injected animals were 18, 11, and 5 percent greater than corresponding control weights. In addition, morphometric analysis of the cerebrum revealed a somatosensory cortex that was 18 percent thicker than that of the controls. The cerebellum of naltrexone-treated rats was 41 percent larger in total area and contained at least 70 percent more glial cells and 30 percent more granule neurons. Neurons derived prenatally were unaffected by drug treatment. These results show that naltrexone can stimulate body and brain growth in rats and suggest a role for the endorphin and opiate receptor system in development.

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Section: Developmentsupporting

confidence: 69%

Section: Developmentsupporting

confidence: 69%

Section: Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Increased Brain Size and Cellular Content in Infant Rats Treated with an Opiate Antagonist

Zagon

McLaughlin

1983

Science

206

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“…Both direct 39 and indirect 18,38 mechanisms of action of exogenous opiates on neural growth have been proposed. In vivo studies showing the ability of morphine to inhibit [ 3 H]thymidine incorporation in rat brain in a naloxone reversible manner 18 , as well as the ability of opiate antagonists such as naloxone 50 or naltrexone 33 to increase [ 3 H]thymidine incorporation in the rat forebrain implies an action at the level of the opioid receptor.…”

Section: Introductionmentioning

confidence: 99%

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

Stiene‐Martin

Gurwell

Hauser

1991

Developmental Brain Research

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SUMMARYTo determine whether exogenous opiate drugs with abuse liability directly modify neural growth, the present study investigated the effects of morphine on astrocyte proliferation and differentiation in primary cultures of murine glial cells. The results indicate that morphine decreases glial cell production in a dose-dependent, naloxone reversible manner. Most notably, gliogenesis virtually ceased in the presence of 10 −6 M morphine during the first week in culture, whereas 10 −8 M or 10 −10 M morphine caused an intermediate suppression of growth compared to control or 10 −6 M morphine treated cultures. Moreover, morphine-treatment inhibited [ 3 H]thymidine incorporation by glial fibrillary acidic protein (GFAP) immunoreactive, flat (type 1) astrocytes, suggesting that the decrease in glial cell production was due in part to an inhibition of astrocyte proliferation. Morphine also caused significant increases in both cytoplasmic area and process elaboration in flat (type 1) astrocytes indicating greater morphologic differentiation. In the above experiments, morphine-dependent alterations in astrocyte growth were antagonized by naloxone, indicating that morphine action was mediated by specific opioid receptors. These observations suggest that opiate drugs can directly modify neural growth by influencing two critical developmental events in astrocytes, i.e., inhibiting proliferation and inducing morphologic differentiation.

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“…Evaluation of organ development by McLaughlin et al [1978] and McLaughlin and has shown that the severe reductions in the weight of such organs as the heart, kidneys, and liver, often related to un dernutrition during lactation, are not seen in animals treated with methadone postnatally. Moreover, the array and magnitude of altera tions in behavioral ontogeny for animals postnatally exposed to methadone and un dernutrition have been reported to differ [Zagon and McLaughlin, 1978a], Evidence from other investigators indicates that al though acute injections of methadone dimin ish the intake of milk in preweaning mice, tol erance to this anoretic action develops rapid ly and, within 5 days of treatment, fluid in take was normal in drug exposed pups [Smith et al, 1977]. Finally, using a limb regenera-tion model.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Postnatal Undernutrition and Methadone Exposure on Protein and Nucleic Acid Contents of the Brain and Cerebellum in Rats

Zagon

McLaughlin

1982

Dev Neurosci

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The neurochemical effect of postnatal exposure to methadone (METH), undernutrition (UND), and methadone and undernutrition (METH-UND) on the whole brain and cerebellum were examined in 21- and 60-day-old rats. At 21 days, body weight reductions of UND and METH-UND rats exceeded that of the METH animals. However, METH rats had the most severe deficits in the weight and total DNA content of the brain and cerebellum, as well as in brain DNA concentration. All experimental rats were subnormal in body weight at 60 days, as was the brain weight of METH-UND rats. Total brain DNA content was most reduced in 60-day-old METH animals, whereas brain RNA content and cerebellar DNA content was only lower in UND and METH-UND animals. These results suggest that methadone often has a greater retarding effect on whole brain and cerebellar development than would be expected by reduced caloric intake alone, and that at least part of the growth inhibiting effects of this drug originates from nonnutritional causes.

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Inhibition of growth in young mice treated with d,l-methadone

Cited by 41 publications

References 5 publications

Increased Brain Size and Cellular Content in Infant Rats Treated with an Opiate Antagonist

Increased Brain Size and Cellular Content in Infant Rats Treated with an Opiate Antagonist

Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation

Comparative Effects of Postnatal Undernutrition and Methadone Exposure on Protein and Nucleic Acid Contents of the Brain and Cerebellum in Rats

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