Bernhard Jänicke

Motor performance achievements in rats of different ages.

Motor performance of rats of different ages was determined in a cross sectional study. The design includes a test battery of seven motor tasks of graduated complexity. The results show a hierarchical order of impairments of motor functions in aging rats; that is, the more complex the task requirement, the earlier and more pronounced is the susceptibility to deterioration of motor coordination. In spontaneous activity and swimming no difference could be observed between young and old rats. With increasing requirements for the tilting-plane, horizontal wire, climbing and chimney tests as well as the rotarod test, the older rats show a differentiated decrease in performance. The findings are discussed in respect to the theory that aging is a reverse process of early development.

Changes in motor activity with age and the effects of pharmacologic treatment

In a previous study the decline in the motor performance of old rats was determined to be differential. In this study, whether, and to what extent, this decline can be pharmacologically influenced was tested. Therefore, 27 month old rats were orally treated with several nootropics and d-amphetamine for six weeks. Food and water intake were determined. The rats were tested on spontaneous activity and on the tilting plane, climbing, and rotarod tests. The results showed that the nootropics only effected pronounced improvements on complex motor tasks such as on the rotarod test. In contrast, amphetamine treatment caused rather negative effects. This could be observed in the motor performance as well as in the food and water intake. Young rats did not have this sort of reaction to amphetamine. The nootropics were all well tolerated. Additionally, it was obvious that the untreated rats also showed a slight improvement in motor performance due to repeated practice.

The effects of prenatal exposure to hypoxia on the behavior of rats during their life span.

The aim of this study was to investigate the influence of moderate prenatal damage on adaptability during the juvenile, adult, and senile phases. Pregnant rats were exposed to a 12% normobaric hypoxia from day 1 to 17 postconception. Pregnancy was normal in both the treated animals and the controls. Erythrocytes, hemoglobin, and hematocrit did not increase in the treated pregnant animals. During the first 3 weeks, the F1 generation showed developmental deviations in physiological characteristics. Throughout subsequent ontogeny, motor performance, cognitive ability, and adaptability to physical stress were determined with a test battery of varying demands. Some of the differences (e.g., locomotor activity, learning ability) between juvenile untreated and treated rats disappeared during the adult phase. Motor and coordinative abilities, however, remained partially impaired in the old rats, especially under high demands. This study, and previous findings with alcohol (37), indicate that prenatal exposure to a noxa may result in a highly differentiated brain injury pattern. Depending on the different functions, damage may intensify age-dependent adaptive disorders or provoke impairment without influencing the course of development.

Effects of chronic hypoxia on behavioral and physiological parameters.

Aging is a process accompanied by progressive susceptibility to disturbances and impairments in adaptability. The influence of age on the capacity to adapt to chronic normobaric hypoxia (10%) was studied in 4, 20 and 27 month old rats. Adaptation was measured for four days by food and fluid intake and spontaneous activity. In addition the values of the pO2, pCO2, pH-value, Na+ concentration and hematocrit were determined. The results show an initial marked decline for the three modalities of behavior in all age groups. While age-dependent differences were exhibited, for the adaptation course in nourishment and spontaneous activity, the values of the blood gases and hematocrit did not reveal age-related changes. Thus, physiological parameters and behavior are not consistent regarding the effects of age on adaptation capacity.

Learning abilities of rats in multiple T-mazes of two degrees of complexity under the influence of d-amphetamine

The effect of d-amphetamine on the learning capacity of male Wistar rats was investigated in multiple T-mazes in two experiments of increasing or decreasing degree of difficulty. Running speed, distance covered and the number of errors were scored to indicate proficiency and success of learning. These parameters, as well as the distribution of errors (goal-directed orientation), correction of errors (situational orientation) and latency at the decision points (discrimination time) were considered to represent cognitive components. The results demonstrated an experiment effect in that the rats showed more difficulty in learning, as exhibited by a slower running speed and more errors, in the maze with successively increasing demands than in the one with decreasing demands. Oral self-administered d-amphetamine in a dosage of 3-4 mg/kg/day or 7-8 mg/kg/day significantly increased the running speed in a dose-dependent manner. By contrast, success of learning and goal-directed orientation decreased. Situational orientation was, however, dose-dependently improved, at least in the experiment with the increasing demand.

The influence of brain catecholamines on 'drug taking behaviour' relative to oral self-administration of d-amphetamine by rats.

Oral administration of 5 mg/kg of d-amphetamine to adult Wistar rats caused brain NE to decrease to approx. 80% of the control level during 4-24 h after acute treatment and slowly further to 65% after 24 days of self-administration via drinking water. The norepinephrine (NE)-reducing effect was first recognized at 1 mg/kg and appeared to peak at 5 mg/kg of d-amphetamine. Brain dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were only shortly affected. Neither iprindole nor desipramine altered the effect of amphetamine on brain NE. DA was decreased by both inhibitors depending on the duration of pre-treatment. Iproniazid and alpha-methyl-p-tyrosine antagonized and potentiated respectively the amphetamine effect on NE- and DA-concentration after 4 days of simultaneous treatment. In the free choice experiment (water vs. 0.005% d-amphetamine solution) rats developed an aversion to amphetamine. The number of rats taking the drug and the consumption by rats still drinking it declined gradually from 100% and approx. 3 mg/kg/day to 50% and approx. 1.5 mg/kg/day, respectively, during 18 days. The time course of the developing aversive reaction to oral amphetamine ran approximately parallel to that of NE-depletion. Iprindole and desipramine intensified, iproniazid and propranolol weakened, while alpha-methyl-p-tyrosine and haloperidol hardly influenced the aversive effect of amphetamine. It is concluded that the development of aversive behaviour in response to oral d-amphetamine is mediated not only through the depleting effect of amphetamine on NE stores but also by its direct stimulation at beta-adrenergic receptors in the CNS.

Influence of normobaric hypoxia on learning capacity of different aged rats

In this study it was tested to what extent subchronic normobaric hypoxia (10% oxygen by volume) influences the learning performance of rats of different ages (4, 20, 30 months). The animals were presented with two successive conditioning patterns (FR 10/DRL). After acquisition of the FR 10 under normoxic conditions in a Skinner box the rats needed to reestablish the learned behavior under normoxia and further under hypoxia. Following this, the rats had to learn the DRL in a test chamber under the conditions of reduced oxygen. Their performance was compared with that of control animals which had to accomplish the tasks under normoxia. No age differences were observed under normoxia in learning the FR 10. However, the reestablishment of FR 10 under hypoxic conditions was less well performed by old rats than younger ones. The young rats (4 months) had a high efficiency level on the DRL-schedule under normoxia which was not impaired by hypoxia. The old rats (30 months) had considerably lower performance level under normoxia which was not further reduced in individuals by hypoxia. The performance of the middle group (20 months) was, under normoxia, at an intermediate level, while oxygen reduction led to a pronounced reduction in efficiency.

Tests in Rodents for Assessing Sensorimotor Performance During Aging

Abstract One characteristic feature of aging in all organisms is the continuous loss of adaptability to environmental perturbations. It is the result of a loss of control over the harmonization of a number of individual reactions which should be in a reciprocally interdependent state ensuring homeostasis. This chapter includes six sections which describe some sensorimotor performance tests that can be used to closely analyze age-related diminishing adaptability. The subareas which regulate and safeguard the functional systems for which the tests are models, are also presented. Procedures for measuring reflexes, muscular strength, motor activity and coordination are described by means of examples, in addition to some methods which are suitable for assessing motor behavior associated with cognitive abilities or the expression of emotional reactions. The concluding chapter discusses the possibilities and limitations of the tests for describing the scheme of stimulus-effect relationships (stimulus perception – central nervous system processing of information – responsiveness of the target organ) and stresses the need for an extensive battery of tests.

P-Hydroxy-norephedrine as a possible mediator causing the reduction of oral intake of D-amphetamine in rats

In rats D-amphetamine is predominantly metabolized by hydroxylation to p-hydroxy-norephedrine (p-HNE); in guinea pigs, however, by deamination to benzoic acid. After 2-3 days on dosages of 1 mg/kg per day and more rats begin to reduce their oral intake of the stimulant whereas guinea pigs do not. In the present study we examined the hypothesis that the formation of p-HNE in the CNS is partially responsible for this aversion. To determine the elimination of D-amphetamine and the increase in p-HNE, groups of male Wistar rats were given various doses (0.5-5 mg/kg per day) of D-amphetamine in their drinking water intragastrically and intravenously. D-Amphetamine in the brain was determined by radioimmunoassay, p-HNE by high performance liquid chromatography followed by electrochemical detection. In contrast to the concentration of D-amphetamine, the p-HNE-content is independent of the route of administration; after oral treatment it showed a linear increase. The results reveal that p-HNE induces the aversion to the stimulant and that the ratio of D-amphetamine to its metabolite determines the onset of this aversion. No p-HNE was found in the brain of guinea pigs. Guinea pigs do not show any aversion to drinking D-amphetamine solutions, even in high dosages.