Teratogenic effects of methamphetamine in mice and rabbits

Kasirsky, Gilbert; Tansy, Martin F.

doi:10.1002/tera.1420040203

Cited by 44 publications

(26 citation statements)

References 3 publications

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“…Four separate but identical studies, using 13 rabbits, were performed to confirm this, because our data were discordant to those of K asirsky and T ansy [2]. Intravenous administration of 2.5 mg/kg elicited no lethality and was used in study 5.…”

Section: Pharmacologysupporting

confidence: 60%

An Animal Model for the Evaluation of Drug-Induced Chromosome Damage

Amarose¹,

Schuster²,

Müller³

1973

Oncology

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Cytogenetic analyses of cells subjected to psychotropic drugs are important but restrictive when man is the study subject. An experimental animal system, using the rabbit, was established to ascertain whether a relationship exists between in vivo administration of drugs of abuse and chromosome damage. This report describes the cytogenetic data after acute and/or chronic intravenous administration of d-methamphetamine-HCl, LSD-25, and mitomycin C. The hyperthermia data of LSD-25 were analyzed during the experiments with this drug. A positive control was established with mitomycin C and sterile injectable saline was used for the negative controls. Pre and post chromosome complements failed to show any statistical association between chromosome damage and LSD or methamphetamine. The hyperthermia engendered after the injection of LSD was statistically significant and residual in nature.

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Section: Pharmacologysupporting

confidence: 60%

An Animal Model for the Evaluation of Drug-Induced Chromosome Damage

Amarose¹,

Schuster²,

Müller³

1973

Oncology

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“…A rabbit model was chosen for these studies for a variety of reasons: (1) the prior history of the rabbit as a model of behavioral teratology following drug treatment (Denenberg et al, 1982;Hartman, 1974;Hudson and Distel, 1986;Kasirsky and Tansy, 1971); (2) rabbits exhibit patterns of brain development and growth that parallel those of humans (Harel et al, 1972;Hartman, 1974); (3) the rabbit metabolizes dopamine, the neurotransmitter through which cocaine is believed to act, in a similar manner to that in humans and other primates (Reader and Dewar, 1989); (4) the ease of performing multiple intravenous injections of cocaine via the marginal ear vein of the rabbit and thus mimicking the pharmacokinetics of smoking "crack" cocaine, the primary route of administration by pregnant women (Jones, 1990); (5) the sensitivity of the rabbit to the behavioral effects of various drugs is quite similar to that of humans (Denenberg et al, 1982;Harvey, 1987;Schindler and Harvey, 1990); (6) classical conditioning of the rabbit's nictitating membrane (NM) response has become a standard method for examining associative learning and has been demonstrated to exhibit all of the cognitive processes that have been observed in humans (Harvey, 1987;Romano and Harvey, 1992); and (7) the rabbit has been extensively employed to examine the electrophysiological correlates of learning (Gabriel, 1990).…”

Section: The Rabbit Model Of Prenatal Cocaine Exposurementioning

confidence: 99%

Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

et al. 2001

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Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the pharmacokinetics of crack cocaine in humans. At this dose, cocaine had no effect on the body weight gain of dams, time to delivery, litter size and body weight or other physical characteristics of the offspring. In spite of an otherwise normal appearance, cocaine-exposed neonates displayed a permanent impairment in signal transduction via the D1 dopamine receptor in caudate nucleus, frontal cortex and cingulate cortex due to an uncoupling of the receptor from its associated Gs protein. This uncoupling in the caudate nucleus was shown to have behavioral consequences in that young or adult rabbits, exposed to cocaine in utero, failed to demonstrate amphetamine-elicited motor responses normally seen after activation of D1 receptors in the caudate. The cocaine progeny also demonstrated permanent morphological abnormalities in the anterior cingulate cortex due to uncoupling of the D1 receptor and the consequent inability of dopamine to regulate neurite outgrowth during neuronal development. Consistent with the known functions of the anterior cingulate cortex, adult cocaine progeny demonstrated deficits in attentional processes. This was reflected by impairment in discrimination learning during classical conditioning that was due to an inability to ignore salient stimuli even when these were not relevant to the task. The impairment in discrimination learning also occurred in an instrumental avoidance task and could be shown to be due to an impairment of cingulothalamic learning-related neuronal coding. It was proposed that the selective loss of D1-related neurotransmission in the anterior cingulate cortex prevented an appropriate activation of GABA neurons and thus a loss of inhibitory regulation that is necessary for processes involved in associative attention. Taken together, these findings suggest that the uncoupling of the D1 receptor from its G protein may be the fundamental source of the anatomic, cognitive and motor disturbances seen in rabbits exposed to cocaine in utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with the recent reports indicating that persistent attentional and other behavioral deficits may be evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.

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“…If gluco corticoids are excessively secreted in grouped animals, they could also exert a teratogenic action on the embryo [18]. Repeated MAMP treatments as a stress may decrease food and water intake of pregnant animals and affect fetal development [1], These physiological al terations caused by maternal treatment with MAMP could potentiate the direct terato genic effects of the drug in vivo, although fur ther studies are needed to elucidate the mech anisms underlying the difference between in vivo and in vitro teratogenicity of MAMP.…”

Section: Discussionmentioning

confidence: 99%

“…According to official statistics in Japan, the average number of peo ple arrested for abuse of the drug has been about 18,000 per year during the last 5 years, and about 20% of them are females. Since MAMP is teratogenic in mice [1,2], its abuse by females of child-bearing age has been a major concern.…”

Section: Introductionmentioning

confidence: 99%

Effects of Methamphetamine on Rat Embryos Cultured in vitro

Yamamoto

Yamamoto²,

Abiru³

et al. 1995

Neonatology

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Wistar rat embryos were explanted on day 10.5 of gestation and exposed in vitro to methamphetamine (MAMP)at a concentration of 0.1 0.2,0.4,0.6, or 0.8 mM for 24 h, and the direct teratogenic effects of the drug on rat embryos were examined. The viability of cultured embryos was not affected by the MAMP treatment. The yolk sac diameter was reduced at MAMP concentrations of 0.6 and 0.8 mM. The crown-rump length and the somite number of the embryos decreased significantly and dependently on the MAMP concentrations at 0.4-0.8 mM. The protein content was also significantly reduced at 0.4-0.8 mM. The developmental score was decreased in a concentration-dependent manner. The frequency of malformed embryos significantly increased at 0.6 and 0.8 mM. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histological changes such as derangement and necrosis in the neuroepithelial tissue were observed in embryos exposed to high concentrations of the drug. Our results revealed the direct embryotoxic and teratogenic effects of MAMP in the rat.

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Teratogenic effects of methamphetamine in mice and rabbits

Cited by 44 publications

References 3 publications

An Animal Model for the Evaluation of Drug-Induced Chromosome Damage

An Animal Model for the Evaluation of Drug-Induced Chromosome Damage

Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

Effects of Methamphetamine on Rat Embryos Cultured in vitro

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