Behavioral Effects in Laboratory Animals

Deficient leeirning abilities, deficits in the ability to solve complex spatial mazes md impairments in visual discrimations, motor coordination, and reflex development have been reported in postnatally Pb-exposed cmimals, all of which may be antilogous to the lowered IQ and deficits in 

A series of behaviors suggesting deficient response inhibition is also seen following developmental Pb exposure. Specific behavioral deficits are seen on tests of passive avoidance, one way active avoidance, differentied reinforcement of low rates of responding (DHL-EO) and fixed interval schedules of operant controlled behavior operant extinction and operant response inhibition, spontaneous cdternation, and various discrimination reversal problems have also been observed following developmental Pb exposure. 

The above studies suggest that exposure of the developing laboratory animal to Pb can result in both subtle and specific behavior indicators of CNS dysfunction. Unfortunately, a lack of standardization of the time, duration, method, and level of Pb exposure, the species and strain used and the method of behavioral assessment, as well as the presence of undemutrition at high levels of Pb exposure have made the development of unified fonnula-tion of Pb-induced neurobehavioral deficiency difficult. The interested reader is referred to Bomschein et al. and Jason and Kellogg for more extensive reviews of the behaviored effects of Pb exposure in laboratory animals. 

Severed behaviored responses of Pb appear to confortn to a dose-response relationship. For example. Petit and his coworkers have shown that the behavioral alterations of animals exposed to moderate levels of Pb are generally intermediate between those seen in high Pb-exposed animals and controls. Therefore, the differences in levels of Pb exposure may also explain some of the discrepant behavioral findings (e.g., activity changes) observed in different studies. 

A number of behavioral changes observed following Pb exposure are very similar to those seen following hippocampal lesions. 

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It should be further noted that the effects of nerve agents on GABAergic transmission in the CNS may have imph-cations for behavioral effects in laboratory animals and humans, and may also contribute to the induction of convulsions at higher doses (Bakshi et al, 2000). Nevertheless, given the present undefined application of non-cholinergic data to whole-body estimations, reliance on the primary assumption of AChE action is consistent with recognized opinion (Bakshi et al, 2000). 

It. should be further noted that the effect.s of nerve agents on GABAergic transmis.sion in the CNS may have profound iinplieation.s for behavioral effects in laboratory animals and humans and may also contribute to the induction of... 

Mattei, R., R.F Dias, E.B. Espinola, E.A. Carlini, and S.B.M. Barros. 1998. Guarana (Paullinia cupana) Toxic behavioral effects in laboratory animals and antioxidant activity in vitro. J. Ethnophatmacol. 60(2) 111-116. 

Two developments led neuroscientists as well to reexamine aluminum as a potential neurotoxicant. One was the discovery that aluminum played a role in the encephalopathy associated with kidney dialysis. The other was the implication that it was associated with senile dementia of the Alzheimer type. The connection with dialysis encephalopathy has been established, although a suitable animal model is lacking. The association with Alzheimer s disease is tenuous, but the issue has stimulated a considerable body of work that both illuminates the biological actions of aluminum and provides further knowledge of degenerative processes in the nervous system. The behavioral data in laboratory animals are ambiguous because, to achieve effects, many experimenters have administered the aluminum intracranially, a mode of administration with obvious pitfalls. A useful summary of the recent literature appears in the volume edited by Liss. ... 

Many household products contain neurotoxic chemical mixtures. These include fragrance products [111], marking pens [112], and air fresheners [113]. These products contain mixtures of lipophilic and hydrophilic chemicals and exposures in home use are typically far below the TLVs of any of the individual chemicals. Exposures to these products, however, in test chambers produce unpredicted behavioral abnormalities in laboratory animals including altered gait, loss of balance, hypoactivity, tremors, and other symptoms. Though no specific human neurotoxic effects have been noted, these studies suggest that neurotoxic impacts on people are likely. 

In a series of well-controlled studies, anti-sense oligonucleotides administered intraven-tricularly selectively inhibited dopamine type 2 receptor expression, dopamine type 2 receptor RNA levels, and behavioral effects in animals with chemical lesions. Controls included randomized oligonucleotides and the observation that no effects were observed on dopamine type I receptor or RNA levels (142-144). This laboratory also reported the selective reduction of dopamine type 1 receptor and RNA levels with the appropriate oligonucleotide (227). 

Significant sublethal effects of mercury include an increased frequency of cancers, birth defects, and chromosomal aberrations in laboratory animals and wildlife. Adverse sublethal effects of mercurials also include growth inhibition, abnormal reproduction, histopathology, high mercury accumulations and persistence, and disrupted biochemistry, metabolism, and behavior. These - and other aspects of exposure to various mercurials by living organisms - are documented and discussed for representative species of bacteria and other microorganisms, aquatic and terrestrial plants and invertebrates, fishes, amphibians, birds, and mammals. 

Biosynthesis The biosynthesis of the L. a. has not been completely elucidated. Since Lycopodium species cannot or can only be cultivated with difficulty, tracer experiments must be performed at the natural locations. It is certain that the biogenetic building blocks for the complex ring systems are lysine and acetate. Pharmacological activity The L. a. are moderately toxic. Some L. a. are purported to be potent inhibitors of acetylcholine esterase. Huperzine A has attracted attention on account of its stimulating effect on learning and memory behavior in laboratory animals. In Chinese traditional medicine various Lycopodium species are used to treat skin diseases and as a tonic. 

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