Non-trained Animals Research Articles

Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus

The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p < 0.01) improved motor performance, compared to treadmill and nontrained animals. Animals with up to 28 days of simple exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity.

Benefits of moderate training to the nonspecific immune response of colts.

The aim of this work was to assess whether progressive training caused an improvement in the nonspecific immune response of colts because several unusual infections are due to defects inherent in the neutrophilic function among which respiratory diseases are a major defect in the performance of athletes taking part in professional sports activities. A group of 7 Anglo-Arabian colts belonging to the Army was selected. These animals carry out training programmes for their participation in National Jumping Competitions. During a submaximal exercise test (heart rate 150 beats/min and lactate levels maintained at aerobic-anaerobic threshold of 3 mmol/l), they were compared with 5 colts of the same breed, just beginning training exercises. Immediately after the test, the nonspecific immune capacity of neutrophilic polymorphonuclear cells was valued by adherence, chemotaxis, ingestion and digestion of foreign substances tests. The results showed significant differences between trained and nontrained animals for the adherence and foreign particle digestion tests and, beginning with a greater adherence in untrained animals, a superior effectiveness was achieved in the immune function in trained colts, whose digestive capactiy was increased with respect to the untrained ones. It was, therefore, concluded that moderate training and exercise improves and reinforces the response of the nonspecific immune system against future infections in the organisms.

Permanent alteration of muscarinic acetylcholine receptor binding in rat striatum after circling training during development

We evaluated the effect of circling training (CT) in the expression of muscarinic acetylcholine receptor (mAchR) in developing rat striatum. For this, male and female rats were subjected to CT at 20, 30, 40 and 60 days of age during 7 days. Animals trained at 30 days but not at other ages showed an average decreased binding to mAchR of 33% in males and 24% in females, representing a significant difference with respect to control non-trained animals (males P < 0.001, females P < 0.005), and showing also a differential response between sex ( P < 0.01). mAchR drop was found invariably either 2 months or 1 year after training indicating a long term plastic change due to circling training. Scatchard analysis showed that altered binding represents a variation of the total receptor number instead of its binding affinity, with no significant differences found among K d ( P > 0.1). mAchR variation was correlated with the motor performance accomplished in the test. Regarding total distance run, male rats trained for 3 days (300 meters run), for 5 days (600 meters) and for 7 days (900 meters) showed a drop of 19, 28 and 33% respectively ( r 2 = 0.91, P < 0.001), while female changes were of 21, 23 and 24% ( r 2 = 0.78, P < 0.001). Nevertheless, no correlation with running speed was found ( r 2 = 0.13 male, r 2 = 0.02 female; P > 0.1). In summary, these results demonstrate the presence of a limited sensitivity period during striatum development where mAchR expression may be affected by the activity performed during CT, representing a permanent alteration of the receptor levels.

Effects of partial lesion of dorsal hippocampal afferent and GM1 ganglioside treatment on conditioned emotional response and hippocampal afferent markers in rats

Acquisition of the conditioned emotional response (CER) in 32 male hooded rats previously learned to press a bar for food and divided into four groups was studied. Two groups received electrolytic lesion of the dorsal hippocampal afferent and were thereafter injected either with GM1 ganglioside (30 mg/kg daily) or with buffer. Two remaining groups were sham operated and similarly injected. The partial hippocampal deafferentation evoked immediate enhancement of bar presses rate which persisted during the 2-week period of testing. CER training undertaken 2 days after surgical procedures appeared unsuccessful, whereas similar training with a cue of different modality initiated a week later resulted in acquisition of conditioned suppression of bar presses in all groups. Toward the end of training the conditioned suppression was more pronounced in lesioned than in control rats. The GM1 injections attenuated the conditioned suppression in control rats, presumably due to an antinociceptive role of ganglioside treatment. Behavioural training did not change the normal distribution pattern in cholinergic and serotonergic hippocampal afferent markers showing dorso-ventral gradient along longitudinal axis. The lesion-induced decrease pattern was also not affected. However, in contrast to previous findings in non-trained animals, the GM1 treatment was not effective in protecting against degenerative changes in the hippocampus of trained rats.

Blood pressure responses to LBNP in nontrained and trained hypertensive rats

To study the influences of 16 wk of endurance training on the reflex regulation of resting blood pressure, nontrained (NT) and trained (T) female hypertensive rats (SHR) were subjected to conditions of lower body negative pressure (LBNP). Measurements of muscle cytochrome oxidase activity and run time to exhaustion indicated that the animals were endurance trained. The rats (NT = 6, T = 7) were tranquilized with 300-600 micrograms.kg-1 diazepam (IV) before heart rates and blood pressures were measured over a range of 2.5-10.0 mm Hg of negative pressure. When subjected to conditions of LBNP, the reflex tachycardia of the T group was greater than the NT at the lower (-2.5 and -5.0 mm Hg) negative pressures. Although arterial pressure declines were similar in both groups, the T group experienced significantly less of a decline in central venous pressure than the NT animals. When chlorisondamine was used as a ganglionic blocker (2.5 mg.kg-1, IV), the fall in CVP at 10 mm Hg negative pressure was greater for the NT group while the fall in the initial systemic arterial pressure was more for the T group. From these results we concluded that training had altered the interaction between cardiopulmonary and arterial baroreflexes in these hypertensive rats and a nonneural component had been altered such as cardiac function.

Habituation and inhibitory avoidance training alter brain regional levels of benzodiazepine-like molecules and are affected by intracerebral flumazenil microinjection.

The effects of habituation and inhibitory avoidance training on the rat brain regional levels of benzodiazepine (BZD)-like molecules and on central type BZD binding sites were examined. BZD-like immunoreactivity was decreased by 26-50% in the amygdala, cerebral cortex and septum of rats sacrificed immediately after stepping-down from the platform of an inhibitory avoidance apparatus (non-trained group) as compared to naive controls. Rats submitted to a second step-down session 20 h later (habituated group) have significantly lower BZD-like immunoreactivity in the septum (-60%) as compared to non-trained animals. Rats exposed to an inhibitory avoidance training, i.e. stepping-down and receiving a footshock (trained group), showed a significant reduction in the content of BZD-like molecules in cerebral cortex (-44%), amygdala (-68%), septum (-80%) and hippocampus (-82%) as compared to non-trained rats. In addition, the density of central type BZD binding sites was slightly increased in the hippocampus and septum of trained rats. No changes were observed in the apparent dissociation constant. No changes were observed in parallel measurements of [3H]-L-quinuclidinyl benzylate binding constants at cholinergic muscarinic binding sites. The immediate posttraining intrahippocampal bilateral injection of the central type BZD receptor antagonist flumazenil (10 nmol/hippocampus), enhanced the retention of habituation but not when injected in the amygdala or septum. In contrast, retention of the inhibitory avoidance task was significantly increased by flumazenil administered bilaterally into any of the 3 brain structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary cis-fatty acids that increase protein F 1 phosphorylation enhance spatial memory

Activation of protein kinase C (PKC) facilitates long-term potentiation (LTP), a model of memory, and increases its substrate protein F 1 (aka GAP43) phosphorylation in direct relation to synaptic enhancement. Unsaturated fatty acids (c-FAs) which activate purified PKC, when injected into hippocampus, enhance LTP. To determine if dietary c-FAs could alter memory itself as well as brain PKC substrate (F 1) metabolism, rats were maintained for 10 weeks on fatty acid diets enriched in mono-unsaturated oleic acid (OA; 20% olive oil, w/w), or a mono- and di-unsaturated mixture of oleate/linoleate (O/L; 20% corn oil), or a saturated fatty acid diet of laurate/myristate (L/M; 20% hydrogenated coconut oil). The O/L diet group was superior to the OA and L/M groups in spatial memory performance after the first two weeks of acquisition and in later achievement of criterion performance. The O/L diet had a significantly higher hippocampal protein F 1 in vitro phosphorylation than in both the OA and L/M in trained and non-trained animals. Significantly, animals that made fewer errors showed higher F 1 phosphorylation ( r = −0.70). Diet both increases brain PKC substrate phosphorylation and enhances maze learning, confirming the feasibility of enhancing learning and memory by dietary regimens derived from basic neurochemical studies of synaptic plasticity.

Forgetting of a conditioned emotional response and its alleviation by pretest amphetamine

Rats were given a single footshock after stepping through from a white to a black compartment. Retention was evaluated in terms of step-through latencies, darkness preference, and pattern of locomotor and exploratory activity, comparing behaviors of trained and nontrained animals 24 h after shock. Forgetting was seen at 25 days after training. Treatment with.5 mg/kg amphetamine before retention test alleviated the forgetting, but had no effect on darkness pbl]References or patterns of activity in either nontrained animals or animals tested at 24 h. In a second experiment, avoidance behavior was again facilitated by pretest amphetamine after a 25-day retention interval, and it was shown that this increased avoidance in drug-treated rats occurred only when shock had been associated with the testing environment; it was not seen in noncontingent-shock groups. The results show that reliable and robust forgetting of a well-Iearned conditioned emotional response can be demonstrated when other than step-through latencies are used as a performance measure. They further support the notion that retrieval processes are labile and that catecholamines may playa role in their modulation.

Effects of endurance training on coronary resistance in dogs

The effects of endurance training on coronary vascular resistance, myocardial blood flow, and oxygen consumption during tachycardia, and with adenosine-induced coronary dilation, were studied in a group of exercise-trained dogs. Seven mongrel dogs were conditioned by 8 wk of running on a motor-driven treadmill. Following conditioning, aortic pressure was unchanged in trained compared to a nontrained group, while cardiac output was somewhat lower in the trained group. Left ventricular myocardial blood flow determined by the microsphere technique was not different at rest or with tachycardia in trained vs control animals, and no significant differences in oxygen consumption were observed between trained and nontrained animals under any experimental conditions. Coronary resistance during pacing (NT: 1.00 +/- 0.09, T: 0.79 +/- 0.06 mmHg/ml X min-1 X 100 g-1) in the trained group was similar to the nontrained group, and both groups had the same resistance during adenosine infusion (NT: 0.49 +/- 0.20, T: 0.44 +/- 0.08). In addition, there were no differences in coronary A-V oxygen difference or coronary sinus saturation after training. The data indicate that little change occurs in the maximum flow capacity of the coronary bed following exercise training, and the trained heart responds to tachycardia with a reduced vascular resistance and increase coronary flow in a fashion similar to untrained animals.

Endurance training attenuates stress hormone responses to exercise in fasted rats.

Endurance exercise training produces major adaptations in hormonal and metabolic responses to exercise. This study was designed to determine whether the differences in hormone response persist in the fasted condition when liver glycogen is depleted. Rats were run on a motor-driven rodent treadmill 5 days/wk for periods up to 2 h/day for 10 wk. Trained and nontrained rats were then fasted 24 h and were run for periods ranging from 0- to 60 min. At the end of 60 min of exercise muscle glycogen was higher in trained rats (2.9 +/- 0.3 vs. 1.1 +/- 0.1 mg/g). Blood glucose was maintained at higher levels in trained rats throughout the course of the exercise (3.2 +/- 0.1 vs. 2.3 +/- 0.1 mM after 60 min). Plasma concentrations of glucagon and epinephrine increased in both groups during the exercise but were significantly lower in trained animals. Differences between trained and nontrained animals in stress hormone responses to exercise persist in the fasted state and appear to be a consequence of the capacity of trained animals to maintain higher blood glucose levels.

Reactivity of limbic neurons of the monkey to appetitive and aversive signals

Monkeys were trained to press separate levers in response to two different visual stimuli. Correct response to one stimulus led to food reward and correct response to the other ensured a diminution of the probability of an electric shock. Thus, in the fully trained animal, one stimulus was used operationally as a signal for food (F) and the other as a signal for shock (S). After training, the animals were surgically prepared for recording of single-unit activity in the awake state by means of a roving microelectrode. Limbic unit discharge and the EEG from limbic structures were recorded during performance of the discrimination task. The results can be summarized as follows. 1. 1. Spontaneous activity of limbic units in the test situation was generally higher among animals performing discrimination than in non-trained animals or in animals subjected to extinction of discriminative behavior. 2. 2. Over one half of all units sampled from the amygdala, the hippocampus and the piriform cortex of trained animals responded with changes of firing frequency to presentation of one or both signals; excitatory responses were more common than inhibitory responses. 3. 3. Reactivity of limbic units, both in magnitude of responses to the signals and in number of responsive units, was higher in animals performing discrimination than in non-performing animals. 4. 4. Units responding differentially to the F signal and to the S signal were observed more frequently in the amygdala than in other limbic structures. 5. 5. The EEG from limbic structures showed non-specific reactions to the signals generally characterized by transition toward frequencies higher than those prevalent in the resting EEG. These results are discussed in the light of knowledge acquired by anatomical, electrophysiological and behavioral research on the limbic system. EEG reactions to the signals are viewed as manifestations of the activation of limbic structures by perception of stimuli with motivational significance for the organism. The described changes of activity of limbic units are interpreted tentatively as phenomena of the participation of these units in the cerebral processing of this kind of information. It is suggested that integrative processing of significant sensory information takes place in successive stages, proceeding from sensory systems, through the inferior and mesial temporal cortex, toward the hippocampus and the amygdala.

Influence of physical training, aortic constriction and exogenous anterior pituitary hormones on the heart weights of hypophysectomized rats.

Studies were conducted with hypophysectomized rats to determine the effects of chronic exercise (training), injections of exogenous hormones, aortic constrictions and combinations there of on the weight of the heart. In addition, the role of growth hormone on cardiac weight was reinvestigated. The hypophysectomized rats that were trained for 10 weeks or longer had significantly heavier heart weights than their nontrained counterparts. When daily injections of a single exogenous hormone of ACTH, GH, ICSH or TSH were made into trained and nontrained animals, there was no trained group that had significantly heavier heart weights than their control group. Rats having aortic constrictions or receiving DOCA injections also had significantly heavier heart weights than their controls. When various dosages of GH (0.2 mg to 6.0 mg) were injected daily for three weeks, no evidence was obtained that indicated that the presence of this hormone resulted in cardiac enlargement. It was concluded that under the experimental condition of this study, cardiac enlargement can occur in hypophysectomized rats when the work demands on the heart have been increased.

The effects of training on myocardial metabolism.

Aerobic and anaerobic activity measured in heart homogenates were generally lower in trained rats than in controls. This depressed activity was not seen in non-trained animals subjected to a single bout of exercise or to chronic aortic coarctation of a degree to simulate “training” hypertrophy. The mildly trained heart also did not spare its endogenous glycogen, as might be expected, during acute exercise.

Hormonal involvement in the reduction of cholesterol associated with chronic exercise.

The involvement of hormones in the reduction of cholesterol associated with chronic exercise was investigated in male rats maintained on a normal diet. Trained or nontrained animals belonging to one of the following groups were used: normal, thyroidectomized, hypophysectomized or hypophysectomized plus thyroid stimulating hormone (TSH). Rats were trained in motor driven treadmills for a minimum of ten weeks and were capable of running continuously an hour a day at a speed of a mile/hour. Significant increases in ligamentous strength indicated that the training program was effective in producing a trained state.

Training and bradycardia in rats.

Bradycardia produced by training was investigated in 228 mature male rats belonging to normal, vagotomized, diencephalon-lesioned, immunological sympathectomized, and hypophysectomized groups. During a 70-day experimental period, resting heart rates of trained unanesthetized rats were significantly lower than those of non-trained rats at approximately 40 days after the training program had been initiated. Resting heart rates were correlated with body weight, wet and dry heart weight, percentage of solids, and the heart weight/body weight ratio (heart ratio). Several coefficients were statistically significant but the majority of the coefficients were below ±0.60 and exhibited a low relationship between the various parameters. Heart ratios for the trained vagotomized, diencephalon-lesioned, and immunological sympathectomized were significantly lower than the ratios from normal trained animals. Similar trends were observed with the nontrained subgroups when these ratios were compared with normal nontrained animals. The only exercising group that exhibited statistical evidence for cardiac hypertrophy was the normal trained group. It was concluded that other aspects beside the weight of the heart must be considered in any satisfactory explanation for this form of bradycardia.