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Biomedical subjects

J Hassmannová

Publications and source records attributed to J Hassmannová.

At least 19 recordsLinked to original sources

Interactions between nitric oxide and dopamine in inhibitory learning and memory in newborn rats.

Taking into account our previous results on dopamine and nitric oxide effects on neonatal inhibitory learning and memory in rats, the mutual interactions of the two molecules were studied in this experimental paradigm. Both increased dopamine content and nitric oxide bioavailability in the brain after application of dopamine and L-arginine as substrate for nitric oxide synthase solutions into lateral cerebral ventricles improved learning and 24 h memory. Joint application of dopamine and L-arginine yielded still more improvement. Learning and memory processing were dose dependently enhanced by D1 receptor agonists as well, whereas D1 receptor antagonists had an opposite and also dose-dependent effect. Dopamine or D1 receptor agonists administered together with nitro-L-arginine, a nitric oxide synthase inhibitor that impaired learning and memory due to a decreased nitric oxide availability, antagonized the effect of nitro-L-arginine, as did L-arginine. D1 receptor antagonists impaired both learning and memory, and L-arginine rendered learning values normal. The dopamine and D1 receptor-agonist effect on 24 h memory was concentration dependent, and their higher concentrations substantially increased the retention indexes. The intimate mechanisms of these interactions are to be identified in further experiments.

Animals

Inhibitory learning and memory in newborn rats influenced by nitric oxide.

The impact of nitric oxide on learning, memory processing and retrieval was studied in the neonatal rats. For comparison, spontaneous motor activity and changes of brain temperature were also studied after nitric oxide manipulations in identical age groups. The nitric oxide availability was either increased by a systemic or intracerebroventricular application of L-arginine, a substrate of nitric-oxide synthase, or decreased by nitro-L-arginine, its inhibitor. L-arginine, 20 mM or nitro-L-arginine, 10 or 5 mM were given intraperitoneally, 1 ml/100 g weight, or in the amounts of 11 into both lateral cerebral ventricles. Intact and saline injected pups were used as controls. Spontaneous motor behavior of newborn pups were not unambiguously affected by nitric oxide, and the same applies to changes of brain and body temperature or heart rate. In no case any correlation with changes of learning and/or memory could be established. Learning was dose dependently impaired relative to controls by intraperitoneal application of nitroarginine. L-arginine only slightly decreased numbers of trials to both criteria and partially abolished the blocking effect of nitroarginine on nitric oxide synthase. With the use of intracerebroventricular injections the positive impact of L-arginine on learning became highly significant. In 24-h memory, intraperitoneal injections of L-arginine enhanced the retention indexes. The impairing effect of nitro-L-arginine significantly increased with delaying after-learning application intervals, being more pronounced at the 3-h than at 0-h interval. Here also, its effect was partially abolished by L-arginine. Effects of nitric-oxide availability in brain after intracerebroventricular application of these substances at 16 various post-learning intervals were assessed on memory processing and retrieval. A general enhancing effect of increased nitric-oxide supply on 24-h retention indexes was found through all studied intervals, which was not, however, monotonous, but several peaks appeared with application at 3, 6, 18 and 23.5 h after learning. On the other hand, the suppressive effect of NArg was not evident relative to saline before the 6-h post-learning injection delay. These results show that nitric oxide exerts a considerable central modulatory effect on learning, memory processing and retrieval at the very early postnatal period of the rat. The efficiency of nitric-oxide manipulations depends on its actual bioavailability in the brain and the stage of memory processing.

Animals

Ontogeny of ribonucleic acid content in rat cortical neurons influenced by early stimulation.

Developmental changes in the total RNA content were studied in pyramidal cells of the frontal, parietal (somesthetic), temporal (auditory) and occipital (visual) cortical areas in Wistar rats aged 13, 14, 15, 21, 28, 35 and 56 days, and compared with those after complex, visual and acoustic stimulation. In all areas neuronal RNA content reached peak values at the age of 3 weeks, except the parietal cortex, where the values were highest as early as at 15 days (in 21-day pups they were only insignificantly lower). Between the age of 3 and 4 weeks, RNA content of cortical neurons decreased in all three projection areas, whereas in the frontal cortex a significant decline came later--in the 5th week. In the occipital cortex neuronal RNA at 8 weeks reached reliably lower values than in 13-day pups. Neuronal RNA increased at the time of eye-lid opening (13-15 days), highly significantly in the visual cortex. Complex visual and acoustic stimulation raised neuronal RNA content in projection areas of modality involved in stimulation and, moreover, acoustic stimulation did so in the frontal and occipital cortex. On the contrary, complex and visual stimulation decreased RNA contents in the frontal cortex. Developmental dependence, stimulation contingency, and specificity vs. nonspecificity of the observed changes are discussed, and compared with other biochemical, morphological and functional changes that have been found in the period of peaking RNA content, or immediately thereafter.

Acoustic Stimulation

Impact of prenatal low-dose diazepam or chlorpromazine on reflex and motor development and inhibitory-learning.

Long-term behavioral effects of a low dose of diazepam (1 mg/kg body weight) or chlorpromazine (2.5 mg/kg) administered 2-3 times during the last week of pregnancy i.m. were studied in Wistar rats and compared with sequelae of analogously applied saline as well as with normal ontogeny in controls. Inhibitory learning-and-memory ontogeny was assessed by 3 types of passive avoidance (PA) at 3 different life periods: neonatal, 2 months, 4 months. Also were investigated: development of righting, air righting, hanging on a thin horizontal bar, eye-lid opening, somatic development and mortality. Prenatal application of diazepam had adverse effects in all parameters except of eye-lid opening. The reflex and motor development was retarded, and so was body weight. The high mortality in the diazepam treated progeny was due to increased death rate in males. In all PA paradigms investigated no memory was established in rats given diazepam prenatally. Chlorpromazine exhibited a lesser effect. I.m. saline had doubtless a character of prenatal-stress. The impact of diazepam was therefore the result of its proper action and only of a partial, if any, after-effect of prenatal stressful manipulation of the dam.

Animals

Step-down passive avoidance in the rat ontogeny.

Ontogeny of step-down passive avoidance (PA) was studied in 174 Wistar rats at the age of 2, 3, 4, 6, 8 and 13 weeks. Latency to the first descent from the safe bench (DL), number of descents (DN), time to criterion meeting (TC) and time during which animals were shocked (TS), were evaluated within learning (L) and two consecutive retention tests (R1 and R2); R1 took place at short to intermediate intervals (5 min-6 h), R2 24 h after learning. None of 2-week pups mastered the task. The most efficient learning was in 6-week pups, and also three indices of R1 (DN, TC and TS) were best at this age. However, the longest DL (most commonly used memory index in PA) was found in R1 and R2 of 3-week pups, due probably to high fear motivation. In 3-month animals DL was zero in R1. It is emphasized that the development of learning and memory is non-monotonous, which was also seen in our previous studies. There were differences between DL recalled from memory and other three indices (DN, TC and TS) in which further reinforcement within the retention test facilitated the retrieval.

Age Factors

Early inhibitory learning in the rat. I. Learning and memory development.

The present status of knowledge on early inhibitory learning and memory is presented. The inhibitory learning (passive avoidance) can be mastered by rat pups several hours after parturition, provided specific characteristics of the newborn organism and its neurobehavioral capabilities are respected. The curve of numbers of trials to criterion displays, as already reported earlier, a generally decreasing trend which is, however, interrupted by a temporary inversion in both strains studied, but at different time, taking place in Long Evans between postnatal day 1 and 2, which is shifted in Wistar pups one day later. Present data show significant learning differences between strains at postnatal days 1-4; from day 5 onward no significant differences are evidenced up to postnatal day 11. A reliable 24-hour memory shown by positive values of the retention index (RI) is revealed from postnatal day 4, having in Long Evans higher RI values. Moreover, high positive RIs of 24-hour memory are found in animals trained on the day just before the inversion of the learning development. It is conjectured that the indirect development of the early inhibitory learning is due to the developmental reorganization within CNS, and the necessity to find out its underlying mechanisms is emphasized.

Aging

Differential ontogenetic peaks and drops in various conditioned reactions.

A survey of results obtained by the authors was compared with the body of recent data of the literature on the development of learning and memory. The following conclusions were pointed out: The development of learning and memory is not a monotonous process; one or more peaks followed by temporary drops or lasting decay are characteristic for it. There is no coincidence in time between learning and memory peaks, both are greatly dependent on the experimental design and conditions. Learning of more complex reactions and prolonged retention intervals shift the peaks toward later age periods. Early learning and memory that occurs at earlier age periods than thought before may be proved in the very first postnatal days in altricial mammals for inhibitory conditioning as well, if neurobiological and developmental specificities of this age are respected.

Animals

The development of inhibitory learning and memory in hooded and albino rats.

A special kind of passive avoidance was elaborated which made it possible to study inhibitory conditioning in hooded (Long-Evans) and albino (Wistar) rat strains from day of birth to 10 or 11 days of age. Remaining on the safe platform for 60 sec, thus avoiding an electrified grid, for the 1st and 2nd time were the criteria. Passive avoidance was established from the first postnatal hours in both strains. A general developmental trend was demonstrated by a decreasing number of trials to both criteria and increase of average latencies. A temporary inversion of this trend in hooded rats took place at the age of 2 days, and in albinos at the age of 3 days. Habituation or fatigue were excluded by control experiments without noxious stimulation, and the associative character of the reaction was further proved by sensitization experiments. Evidence of memory retention was obtained as early as between the day of birth and the next day. The animals which served on the day of birth as controls needed, on the following day, significantly more trials than naive animals or pups which had been taught, one day before, to avoid the electrified grid. This phenomenon was called 'learned safety' for the previously control animals behaved as if they had learned that descent to the grid was safe. The 24-h memory of the learned inhibitory reaction--withholding movements towards the grid--was first observed in hooded rats between 1 and 2 days of age. Thus the capability to learn an inhibitory reaction has been proved in the neonatal rat which is born less mature than many other altricious mammals. Though learning and memory in both rat strains improved with age, there were small differences in favor of their earlier development in pigmented animals.

Aging

Ontogeny of active avoidance in the rat: learning and memory.

Ontogenetic development of active avoidance learning, extinction and retention was studied in rats. The learning of a 1-way active avoidance was most rapid between Weeks 4 and 6, although some slight gender-related differences were evident. No such unambiguous development was detected in forced extinction. The 24-hr retention of avoidance peaked at the age of 4 weeks whereas 1-month retention was best in animals trained at the age of 8 weeks. The retrieval of memory trace also had best values at these ages. Retention of forced extinction was found to peak in 6-week animals. The existence of developmental "critical periods" must be considered cautiously as various functions have different time courses depending upon the chosen parameters in assessment.

Animals