Behavioral effects assays

This third part of the book will be devoted mainly to the problem of addressing complex pollution problems and how they can be studied employing new biomarker assays that exploit new technologies of biomedical science. Chapter 13 will give a broad overview of this question. The following three chapters, The Ecotoxicological Effects of Herbicides, Endocrine Disrupters, and Neurotoxicity and Behavioral Effects, will all provide examples of the study of complex pollution problems. 

Because of their wide-ranging and holistic character, assays of behavioral effects have been used as screening procedures when testing for neurotoxicity (see, for example, Iversen 1991, Tilson 1993). They can provide sensitive indications of neurotoxic disturbances, which can then be traced back to their ultimate cause by using mechanistic biomarker assays. 

In a similar way, an integrated biomarker approach has a role when carrying out experiments in mesocosms. Under these controlled conditions, behavioral effects of neurotoxic pollutants, acting singly or in combination, can be monitored and compared with data on predator-prey relationships and effects at the population level. The employment of mechanistic biomarker assays can facilitate comparisons between results obtained in mesocosms and other data obtained in the field or in laboratory tests. Here is one way of attempting to answer the difficult question— how comparable are mesocosms to the real world ... 

Costall et al. (21) have questioned the relevance of this alpha and beta nomenclature. These workers noted that many of the differences observed between dopamine congeners of the two types in eliciting peripheral and behavioral effects may be attributed to ability to penetrate into the CNS, differential distribution, and differing susceptibility to Inactivation by COMT or MAO. The question of relative potency In comparing alpha rotameric types with beta rotameric types Is heavily dependent on which type of bioassay is employed. This problem is compounded by the fact that a large number of novel dopamine agonist types have not been completely evaluated pharmacologically. Each laboratory seems to have a particular series of assays and it is seldom that a compound is examined in all relevant tests. 

In vivo assays Assess functional or behavioral effects (e.g., blood pressure diuresis pain heart rate respiration pigmentation). 

Ethanol, when given orally to mice at doses of 0.125-2.0 g/kg, potentiated both the lethality and behavioral effects (inverted screen test) of inhaled 1,1,1-trichloroethane at concentrations ranging from = 200 to 10,000 ppm (Woolverton and Balster 1981). In another study, a 3-day pretreatment of mice with ethanol enhanced 1,1,1-trichloroethane-induced liver toxicity, as indicated by an assay of liver function (bromosulfophthale in retention in plasma), but not an assay of liver damage (SGPT levels) (Klaassen and Plaa 1966). Other studies, using only serum enzyme levels to assay liver... 

The behavioral effects of dermal exposure to maneb were studied in adult male Swiss mice (Mitchell et al. 1989). Five mice per dose group were dermally exposed to either 16, 160, or 1,600 mg/kg maneb in a conditioned taste aversion assay. Aversion to a saccharin solution was tested 24 hours following the dermal application of the compound to a shaved area on the mouse s back, immediately caudal to the skull. Maneb application did not affect taste aversion compared to water controls. Activity was measured for both ambulatory and nonambulatory activity ambulatory was when a subject sequentially disrupted at least two adjacent infrared beams in an activity monitor nonambulatory activity was when a subject sequentially broke the same beam. When given at a dose of 1,600 mg/kg, maneb increased the activity levels of a tested group (5 subjects) by 3-fold over controls. When the mice were tested individually, however, there were no... 

Korean traditional preparations Thirty-one naturally occurring substances used to treat psychosis in Korean traditional medicine were subjected to in-vitro CNS screening assays using crude plant extracts. In-vitro assays revealed several CNS receptor selectivities and affinities. More constituents had strong binding affinities with monoamine receptors than other CNS receptors. Controlled animal studies are needed to elucidate specific behavioral effects of different preparations. 

These different considerations have led us to assume that this method would be useful to investigate the behavioral effects of toxicants in preference to more natural approaches such as studies in field or semi-field conditions because it allows better control of treatment and conditioning parameters. Indeed, precise quantification of behavior is essential for determining whether a specific non-environmental variable affects the normal behavior. The sublethal effects of chemical pesticides have already been studied using restrained workers in the CPE assay [32-35]. It remains to establish whether the use of the CPE response as a measure of the sub-lethal effects of chemicals on honey bees can be a reliable indicator of the hazards associated with the exposure to sublethal doses of toxic compounds, and consequently can be included in standard screening proce-... 

Behavioral effects of cannabinoids are usually assessed in adult rodents. However, in vivo assessment of cannabinoid effects in developing animals is important in order to assess the correlation between CB, receptor development with age and their functional (in vivo) expression (84). In addition, in vivo developmental studies help evaluate therapeutic and/or side effects of putative cannabinoid-based (medicinal) drugs in children (85,86). The tetrad developed for assessment of cannabinoid-like activity in adult mice is not suitable for assaying cannabinoid effects in immature rodents. However, several aspects of such function do develop sufficiently that valid assessments of cannabinoid-induced behaviors may be meas-... 

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