Tactile-kinesthetic system of rats as an animal model for minimal brain dysfunction

Abstract

A previous study showed that rats exposed to methylmercury during development exhibit effects similar to those described for children with minimal brain dysfunction (MBD), namely, hyperactivity, altered locomotion structure, and unaltered learning ability, but reduced and more variable attention spans induced by increasing difficulties within an operant learning paradigm. Psychopathological studies suggest that behavioral disturbances of the MBD type may originate directly or indirectly from deficiencies in the tactile-kinesthetic system. This sensory modality is the main mechanism by which an individual organism assimilates reality. Deficiencies in the tactile-kinesthetic system impair the action of the equilibration processes (in Piaget's sense) which ensure that the stages of psychological development occur in an orderly sequence. The lack of this control over development may result in the behavioral characteristics of MBD. Problems with the tactile-kinesthetic system may also be the reason for the deficiencies of fine motor control in MBD children. In an attempt to extrapolate this interpretation of human psychopathological mechanisms to experimental animals, an operant paradigm was developed for the assessment of the tactile-kinesthetic system of rats, the schedule of "differential reinforcement of force range" (DRF). Rats were trained to press in discrete trials a force sensitive lever during at least 1 s between two force thresholds of 60 and 80 g without any feedback other than the rats' own tactile-kinesthetic perception. Offspring of rat dams exposed to 1.5 and 5 mg/l methylmercury-chloride in their drinking water from 2 weeks before pairing until weaning, exhibited a clearcut performance deficit (approximately 25% correct responses compared to approximately 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Windows of sensitivity to toxic chemicals in the motor effects development

“…Similarly, exposure to 0.10 mg/kg/day MeHg hydroxide from gestation to PND 55 resulted in diminished motor function overall. Thus, these chronic Hg exposure studies are consistent with the shorter exposure study by Elsner (1991) included in Fig. 3.…”

Evolution of our understanding of methylmercury as a health threat.

“…On the other hand, more mechanistic analyses of these behaviors might reveal the inherent sensitivities of these tests, which would support the former explanation. It should also be noted that the reproducibility of these test results must be demonstrated; e.g., Elsner (40) could not reproduce the deviation in the spatial alternation task (30) obtained in their first trial, and no laboratory has published rodent behavioral studies that showed effects from the same low level of exposure as was demonstrated in the DRH studies (39).…”

“…For example, the results of the discrete trial spatial alternation task used by Eisner et al (30) were compared to the attention disorder (and minimal brain dysfunction) seen in human children. Testing the tactile-kinesthetic system of rats (40) was suggested by human studies that showed a relationship between attention deficit disorder and poor development of the tactile-kinesthetic system in children. If such a functional analogy could be validated with some appropriate experiments, this type of approach could provide a means to directly predict human behavior on the basis of rodent behavior.…”

Evolution of Our Understanding of Methylmercury as a Health Threat

“…Among others, the spatial alternation test (30), the tactilekinesthetic test (40), and the DRH task (39) showed deviations from control at very low dose levels, At these doses, other simple tests such as those included in a functional observation battery, would fail to show any changes. It is unknown, however, whether such differential sensitivities among the tests reflected the nature of the behavioral tasks per se or reflected the nature of the effect of methylmercury.…”

“…6.4 x 1 (gi) GD 15 "Step-down" passive avoidance 60 Rapid extinction (35) Abbreviations: iv, intravenous injection; sc, subcutaneous injection; gi, gastric intubation; GD, day(s) of gestation. (40) trained rats to press a lever with predetermined ranges of force and time. The impaired performance of methylmercury-exposed rats was considered to be a result of deficit in tactile-kinesthetic systems.…”