Neurobehavioral effects of chronic halothane exposure during developmental and juvenile periods in the rat

Levin, Edward D.; Uemura, Etsuro; DeLuna, Raul; Franks, Pat; Bowman, Robert E.

doi:10.1016/0014-4886(87)90267-6

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…Developmental PCB exposure caused significant impairments in working memory in the RAM in adult rats (Corey et al, 1996). We showed that developmental halothane treatment, which retards synaptogenesis in the hippocampus impaired 8-arm maze exploration and learning when the rats are adults (Levin and Bowman, 1986; Levin et al, 1987; Levin et al, 1991). These studies show that RAM choice accuracy is sensitive to the cognitive impairments caused by a variety of toxicants.…”

Section: Developmental Toxicant Exposure and Long-term Effects On Rammentioning

confidence: 96%

Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery

Levin

2015

Neurotoxicology and Teratology

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Cognitive dysfunction has been found in epidemiological studies to be among the most sensitive impairments associated with developmental exposure to a variety of environmental contaminants from heavy metals to polyhalogenated hydrocarbons and pesticides. These chemicals have been also shown to impair cognitive function after developmental exposure in experimental animal models. The radial-arm maze (RAM) has proven to be a sensitive and reliable way to assess both learning and memory in a variety of species, most often in rats and mice. The RAM is a very adaptable test method that takes advantage of rodents’ instinct to explore new places in the environment to forage. That is, rodents do not need to be trained to run through the maze; they will normally do this from the initial session of testing. Training with differential reinforcement for arm choices provides a more rigorous test of learning and memory. The RAM is quite adaptable for assessing various aspects of cognition. Although the RAM has been mostly used to assess spatial learning and memory, it can be configured to assess non-spatial memory as well. Both working and reference memory can be easily distinguished. The RAM can be run with both appetitive (food reinforced) and aversive (water escape) motivators. The RAM has been found to be sensitive to a wide variety of developmental toxicants including heavy metals such as mercury and pesticides such as chlorpyrifos. There is an extremely rich literature especially with rats showing the effects of many types of brain lesions and drug effects so that the participation of a wide variety of neural systems in RAM performance are known. These systems, notably the hippocampus and frontal cortex, and acetylcholine and glutamate neurotransmitter systems, are the same neural systems that have been shown in humans to be critical for learning and memory. This considerably aids the interpretation of neurobehavioral toxicity studies.

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Section: Developmental Toxicant Exposure and Long-term Effects On Rammentioning

confidence: 96%

Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery

Levin

2015

Neurotoxicology and Teratology

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“…The finding that drug exposure can cause changes in the neurodevelopment is decades old, with an early focus mostly on drugs of abuse such as alcohol [ 32 ] and morphine [ 33 ]. There were few studies on therapeutic exposure to sedatives and anesthetics [ 23 , 24 ]. The discovery of DIDNA was first identified by the Olney lab at Washington University School of Medicine in St. Louis when Ikonomidou et al [ 25 ] found that NMDA antagonist drugs caused widespread apoptotic cell death in the neonatal rat brain.…”

Section: Didnamentioning

confidence: 99%

“…An underlying factor in the alteration of brain development may be drug-induced neurodevelopmental apoptosis (DIDNA). DIDNA was first identified in the neonatal rodent brain, caused by classes of drugs that have N -methyl- d -aspartate (NMDA) receptor antagonist or gamma-aminobutyric acid (GABA) mimetic properties, such as ethanol (which has both properties) [ 13 , 14 , 15 , 16 , 17 ], some drugs of abuse [ 18 , 19 , 20 ], anticonvulsants [ 21 , 22 ], sedatives, and anesthetics [ 23 , 24 , 25 , 26 , 27 , 28 ]. The results of early studies provided evidence that pointed to the fact that this type of neurotoxicity is a major public health concern if agents administered in obstetric and pediatric medicine could have the potential to cause brain damage.…”

Section: Introductionmentioning

confidence: 99%

From Drug-Induced Developmental Neuroapoptosis to Pediatric Anesthetic Neurotoxicity—Where Are We Now?

Creeley

2016

Brain Sciences

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The fetal and neonatal periods are critical and sensitive periods for neurodevelopment, and involve rapid brain growth in addition to natural programmed cell death (i.e., apoptosis) and synaptic pruning. Apoptosis is an important process for neurodevelopment, preventing redundant, faulty, or unused neurons from cluttering the developing brain. However, animal studies have shown massive neuronal cell death by apoptosis can also be caused by exposure to several classes of drugs, namely gamma-aminobutyric acid (GABA) agonists and N-methyl-d-aspartate (NMDA) antagonists that are commonly used in pediatric anesthesia. This form of neurotoxic insult could cause a major disruption in brain development with the potential to permanently shape behavior and cognitive ability. Evidence does suggest that psychoactive drugs alter neurodevelopment and synaptic plasticity in the animal brain, which, in the human brain, may translate to permanent neurodevelopmental changes associated with long-term intellectual disability. This paper reviews the seminal animal research on drug-induced developmental apoptosis and the subsequent clinical studies that have been conducted thus far. In humans, there is growing evidence that suggests anesthetics have the potential to harm the developing brain, but the long-term outcome is not definitive and causality has not been determined. The consensus is that there is more work to be done using both animal models and human clinical studies.

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Long-term effects of developmental halothane exposure on radial arm maze performance in rats

Levin

DeLuna

Uemura

et al. 1990

Behavioural Brain Research

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Neurobehavioral effects of chronic halothane exposure during developmental and juvenile periods in the rat

Cited by 10 publications

References 22 publications

Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery

Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery

From Drug-Induced Developmental Neuroapoptosis to Pediatric Anesthetic Neurotoxicity—Where Are We Now?

Long-term effects of developmental halothane exposure on radial arm maze performance in rats

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