Hyperactivity induced by prenatal administration of methylazoxymethanol: Association with altered performance on conditioning tasks in rats

He, Cannon-Spoor; Wj, Freed

doi:10.1016/0091-3057(84)90240-5

Cited by 36 publications

(7 citation statements)

References 16 publications

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“…MAM treatment produces offspring with severe forebrain microencephaly whereas brain stem regions remain essentially unaltered [54,55], Thus, prenatal MAM is considered to cause a relative hyperinnervation of monoamine nerve terminals in certain brain regions, e.g. cortex, hippocampus and striatum, without markedly altering the total number of mono amine nerve terminals and drastic increases in the concentrations of monoamines in re gions that have atrophied [56,57], These changes to monoaminergic pathways have also unfailingly caused long-lasting and marked increases in spontaneous motor activ ity [58][59][60][61], Thus, we have reasoned that peri natal treatments resulting in the pattern of hyperactivity in spontaneous activity accom panied by a potentiation of the effects of d- at adult ages and may be obtained as either behavioral increases, hyperactivity, or de creases, hypoactivity. At present, we do not understand the relative significance of the production of hyper-/hypoactivity, except in the case of neonatal 6-OHDA where hyperac tivity for locomotion and total activity and hypoactivity for rearing/head dips appear to be strongly dependent upon the severity of the DA depletion in forebrain regions.…”

Section: Prenatal and Postnatal Exposure To Metallic Mercurymentioning

confidence: 99%

Functional Changes Implicating Dopaminergic Systems following Perinatal Treatments

Archer¹,

Fredriksson²

1992

Dev Pharmacol Ther

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A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphctamine- induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine- induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85 % depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.

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Section: Prenatal and Postnatal Exposure To Metallic Mercurymentioning

confidence: 99%

Functional Changes Implicating Dopaminergic Systems following Perinatal Treatments

Archer¹,

Fredriksson²

1992

Dev Pharmacol Ther

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“…Though MAM-treated rats develope normally as mentioned previously, hyperactivities (Rabe and Haddad. 1972;Seo et al, 1979;Kiyono et al, 1980;Hanada et al, 1982;Cannon-Spoor andFreed, 1984: Vorhees et al, 1984;Plonsky et al, 1985) and motor impairment (Ciafalo et al, 1971: Yamamoto andTanimura, 1989) were observed. Spontaneous motor activities in MAM-treated rats showed significant increases only during night time, but not daytime (Nagayoshi et al, 1986: Sanberg et al, 1987Balduini et al, 1989).…”

Section: Neurochemical Correlates Of Abnormal Motor Activity In Mam-tmentioning

confidence: 98%

Neurochemical Correlates of Learning Impairment in Microen‐cephalic Rats Induced by Methylazoxymethanol Acetate*

Tamaru

1994

Congenital Anomalies

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Newborn infants with histogenetic brain malformations can be long‐lived with mental retardation, which is considered a major problem in social medicine. Among these infants with mental retardation, many cases are accompanied by microencephaly. Experimentally induced microencephaly in rats presents a useful model for understanding human cerebral disorders. We have studied how neurochemical changes in the brains of microencephalic rats induced by prenatal treatment with methylazoxymethanol acetate (MAM) can affect their learning abilities. We reported that densities of monoaminergic transmitters in the atrophic cerebral hemisphere (CH; consisting of cerebral cortex and hippocampus) of MAM rats was markedly elevated, but that their total quantity per CH unchanged. As for the ability of operant discrimination learning, MAM rats could discriminate tasks. However, excitatory amino acid receptors, in which N‐methyl‐D‐aspartate (NMDA) is well known to be involved in spatial memory, showed decreased total binding in the CH of MAM‐treated rats. Spatial recognition ability evaluated using an 8‐armed radial maze task was impaired. These results suggest that the condensation of monoaminergic terminals in the atrophic CH of MAM rats may compensate for disability in discrimination learning, but the significant reduction of NMDA receptors may impair spatial memory in MAM rats.

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“…There are other animal models of ADHD involving brain lesions. These include rats exposed to lead (Silbergeld and Goldberg, 1974) or X-ray in infancy (Diaz-Granados et al., 1994;Jensh et al, 1995), and rats that have undergone neonatal anoxia (Dell'Anna et al, 1993) or neurotoxic brain lesions, for example with methylazoxymethanol (Cannon-Spoor and Freed, 1984;Vorhees et al, 1984). Recently we studied mice with microcephaly induced by prenatal administration of cytosine arabinoside (Ara-C).…”

Section: Other Models With Brain Lesionmentioning

confidence: 99%

The dopaminergic system in attention deficit/hyperactivity disorder

Ohno

2003

Congenital Anomalies

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Numerous studies have shown the importance of the mesocorticolimbic dopamine system in the pathophysiology of attention deficit/hyperactivity disorder. However, there has been inconsistency in the findings of those studies. Varied and sometimes contradictory interpretation has been made on the basis of similar results. It is, therefore, still unclear whether the dopaminergic system is hypo- or hyperfunctioning in attention deficit/hyperactivity disorder. The majority of the functional brain imaging studies in both clinical and experimental settings support hypofunction of the basal ganglia which receive abundant dopaminergic afferent. The experimental studies, using dopamine-depleted animals, also support the hypodopaminergic hypothesis, whereas recent studies with the dopamine transporter knockout/knockdown mouse suggest hyperdopaminergic function as the underlying abnormality. In this review we attempt to clarify the issues raised by previous neuroimaging and functional neuroimaging studies. Research involving animal models with genetic traits, genetic manipulation or with brain lesions is analysed, concentrating on the significance of the dopaminergic system in the abnormal behavior of attention deficit/hyperactivity disorder. In addition, the functional state of the dopaminergic system is considered through the speculated mechanism of psychostimulant therapy of the disorder. No final conclusions have been reached regarding the pathological, biochemical and physiological mechanisms responsible for various symptoms. Inconsistency in the findings and their interpretations may indicate the heterogeneity of the pathogenesis of this syndrome.

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Hyperactivity induced by prenatal administration of methylazoxymethanol: Association with altered performance on conditioning tasks in rats

Cited by 36 publications

References 16 publications

Functional Changes Implicating Dopaminergic Systems following Perinatal Treatments

Functional Changes Implicating Dopaminergic Systems following Perinatal Treatments

Neurochemical Correlates of Learning Impairment in Microen‐cephalic Rats Induced by Methylazoxymethanol Acetate*

The dopaminergic system in attention deficit/hyperactivity disorder

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