Role of catecholaminergic mechanisms in regulating the autogenic periodic motor activity of rat pups

In 1-, 2- to 3-, 7- to 8-, and 10-day old intact and spinal rat puppies, studies have been made of the effect of l-DOPA (100 mg/kg, intraperitoneally) on autogenic periodic motor activity in the gastrocnemius muscle. In 1- to 3-day old pups, strong stimulating effect was observed up to a prolonged continuous activity for 5-10 or even more minutes. This effect decreases with age. Traces of the inhibitory effect are observed at early stages in the form of total decrease of the activity. The inhibitory effect increases with age. In all spinal animals, at the background of a decreased activity, stimulating effect of l-DOPA was predominantly observed. Age peculiarities of the effect of l-DOPA are discussed in relation to ontogenetic development of catecholaminergic innervation in rats. It is suggested that stimulating effect of l-DOPA is associated with its action on the descending noradrenergic system, whereas the inhibitory one is mediated by the brain structures.     

Characteristics of autogenic motor stimulation in rat pups

Studies have been made on the organization of the spontaneous motor activity during first 2 weeks of postnatal life of rats Rattus norvegicus (var albin.) by means of prolonged EMG recording from the gastrocnemius muscle and by computer analysis. Complexes of prolonged activity with a period of about 1 min, intracomplex periodicity of short pulses with a frequency 1/sec and periodicity of separate short bursts arranged into series with intervals between them of approximately 8-12 sec were observed. It was found that the main rhythm of these forms of excitation remains relatively unchanged during postnatal ontogenesis. The number of periods filled by series of short bursts decreases in postnatal development of animals, whereas the number of periods of a complete rest lasting for 1 1/2 and more minutes increases. These findings were compared with the development of sleep--wakefulness cycle in early postnatal ontogenesis.     

The effect of 6-hydroxydopamine on the autogenic motor activity of newborn rat pups

At the 1st, 2nd and 3rd days after birth, subcutaneous injections of 6-oxydopamine in physiological solution containing 0.1% of ascorbic acid have been made to rat puppies in a dose 100 mg/kg per one injection. Within first three weeks, electromyographic studies were made on outbursts of autogenic periodic motor activity which is typical of animals at this age. It was shown that at the 3rd day of postnatal life, after 6-oxydopamine administration, total duration of motor excitation is significantly lower, whereas mean duration of the outbursts of continuous activity is lower even at the 7th day. Beginning from the 10th day, these parameters undergo opposite changes at the background of the increase in the number of outbursts and the decrease of intervals between the latter. The data obtained are discussed in relation to the role of catecholaminergic systems in regulation and realization of age dynamics of autogenic motor activity.     

Role of motor activity in the development of hypothyroid rat pups

Studies have been made on the role of the thyroid in the development of rats. In the first group of experiments, newborn rat received within a month mercazolyl which inhibits the activity of the thyroid; in animals of the second group, mercazolyl injections were combined with cold exposures which stimulated motor activity in animals. It was found that hypothyroid rats in both groups exhibit retardation of growth as compared to normal animals. However, retardation is less significant in animals of the second group, as it is indicated by smaller changes in the protein content and total mass of skeletal muscles.     

The action of L-DOPA on the structure of spontaneous motor activity in rat pups

In experiments on 2-3-, 7-8-, 10- and 16-day old rat pups, basic age differences have been observed in the effect of a precursor of catecholamine mediator, i.e. L-DOPA on the activity on the spinal and brain mechanisms of autogenic periodic motor excitation. Strong stimulation of the spinal motor rhythm was observed during the first week. At this period, supraspinal rhythm becomes even less evident. On further development, the effect is an opposite one. In 10- and 16-day rat pups, at the background of total inhibition of the spontaneous activity, administration of L-DOPA significantly increases the activity of supraspinal generator of the motor rhythm. The data obtained reveal ontogenetic changes in regulatory mechanisms of autogenic motor activity.     

Cardiac,respiratory, and motor activity in norm and after activation of catecholaminergic systems in newborn rat pups

Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the activity levels of dopaminergic and noradrenergic systems. To provide an excessive level of catecholamines, the animals were administered individually with L-DOPA (25–100 mg/kg) and with the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpirid). The L-DOPA administration produced a dose-dependent MA enhancement with its subsequent possible conversion into the continuous generalized activity. At P0 the release of monoamines was accompanied by development of weak bradycardia. There was noted a tendency for acceleration of respiration at administration of the low dose both of L-DOPA and of isoamine and for its deceleration at high doses. At P14 the L-DOPA administration was accompanied by deceleration of the heart rate (HR) by 8% and by acceleration of respiration rate (RR) by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of RR by 8% at the low dose and by 21% at the high dose of the agent. At the blockade of D1 receptors, RR remained close to the background values, while at the blockade of D2 receptors it decreased insignificantly. Blockade of D1 and D2 receptors did not cause significant HR changes. Analysis of the HR variability has shown that both after L-DOPA administration and at blockade of dopamine receptors no unidirectional reaction was observed: in 80% of rat pups the portion of nerve mechanisms of HR regulation increased, while in the rest-of sympathetic and humoral factors at a decrease of parasympathetic effects. In all rat pups the isoamine administration was accompanied by a shift of the specter power into the higher frequency area; in 60% of the animals there were enhanced sympathetic effects. At P14 in rat pups after administration both of L-DOPA and of isoamine, the sympathetic nervous effects were predominant. Thus, at P0 both at release of endogenous catecholamines and at their excessive concentration in rat pups there occurs a qualitative change of character of the catecholaminergic effects on functional activity of excitable structures, particularly of those connected with regulation of respiration.     

Blood dopamine beta-hydroxylase activity and noradrenaline levels in the developing white rat.

Dopamine beta-hydroxylase (DBH) (3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating) (EC 1.14.17.1) activity in serum of blood obtained by decapitation of white rats at 19, 20, and 21 days in utero, immediately after birth, and postnatally to 70 days, was measured. Noradrenaline (NA) and DBH in plasma from undisturbed, cannulated, postweaning rats were also assayed. During the last few days in utero and the first 2 postnatal days serum DBH activity tripled and then remained elevated during the suckling period. Upon weaning, serum DBH activity declined at first precipitously and then more slowly, until the adult level was reached around 70 days of age. This postweaning decrease in DBH activity was also observed with the cannulated animals. In contrast, plasma NA levels remained low and constant throughout the postweaning period. In suckling rats treated with 6-hydroxydopamine from 2 to 12 days of age, serum DBH activity decreased to less than half its initial value by day 8. It is suggested that the observed changes in serum DBH activity in fetal and postnatal rats reflect ontogenetic changes in sympathetic nerve terminals and that they are probably not correlated with release of NA.     

Periodic phenomenon in the ECoG of newborn rat pups and its correlation with spontaneous motor activity

In conscious 2-6-day rat puppies, studies have been made on the bioelectrical activity in the visual and sensorimotor cortex. ECG in newborn rat puppies exhibits characteristic intermittence of complexes of the electrical activity with intervals of partial or almost complete absence of the activity in a minute scale. This phenomenon reflects the ancient property of immature nervous system, i.e. a capacity to autogenic periodic excitation. The structure of these complexes may be different, since it reflects the condition of animals at the given moment, the degree of maturation of elements involved in realization of the bioelectrical activity and interrelationship with other parts of the brain. With respect to amplitude-frequency parameters, age dynamics and the relationship to the spontaneous motor activity, four distinct types of complexes were revealed in the ECG of rat puppies during the first week of their postnatal life.     

The motor activity of the chick embryo amnion in the late stages of development. The role of serotonin and noradrenaline]

Experiments with 13- to 19-day-old chicken embryos maintained at 37 degrees C were conducted using direct registration of embryonic movements and amnion pulsation. It is shown that in the non-innervated and lacking blood vessels non-striated-muscled amnion, motoric activity could be observed nearly up to the end of the embryonic development, not only during 5 to 14 days old interval as it was supposed earlier. In accordance with our previous results indicating important role of biogenic amines (serotonin and noradrenaline) in the regulation of motoric activity of the chicken embryo amnion at earlier and middle ages, this study provides some evidences of the humoral regulatory mechanism even at later embryonic stages. After being injected into amniotic fluid of older embryos, the serotonin stimulates and noradrenaline inhibits amnion motoric activity (the both are taken at final concentration of 10(-7) to 10(-6) M). Serotonin's receptors blocator, the cyprogeptadin, suppress while beta-adrenoreceptors' blocator, the propranolol, activates intact amnion motorics ( both are taken at final concentration of 10(-7) to 10(-5) M).     

The role of the pallidum in regulating cortical activity]

Bilateral ablation of the pallidum halves the duration of extinction of conditioned motor food reflexes and contributes to 30 to 50% extinction of the electro-defensive reflexes. Pallidum functional depression by potassium chloride or novacaine leads to a temporary total depression of conditioned motor food reflexes. Depending on the frequency of pallidum stimulation, synchronization or desynchronization of the cortical bioelectrical activity is observed. Ablation of the pallidum in anaesthetized cats results in a high amplitude and low-frequency cortical activity. Injection of large doses of potassium chloride into the pallidum results in a forced running forward which lasts 30 to 40 min. The pallidum is considreed as a structure controlling the cortex activity, which takes part in the mechanisms of sensory information processes in the course of adaptive behaviour.     

The role of Asp-462 in regulating Akt activity

Protein kinase Akt, an important downstream target of phosphatidylinositol 3-kinase, is one of the major survival factors in mammalian cells. It has been shown that phosphorylation of the C-terminal hydrophobic motif is required for Akt activation. The activated Akt then phosphorylates several pro-apoptotic proteins and prevents apoptosis mediated by caspases and the mitochondria. Interestingly, Akt has also been implicated to be a direct substrate of caspases in apoptotic cells induced by Fas (Widmann, C., Gibson, S., and Johnson, G. L. (1998) J. Biol. Chem. 273, 7141-7147) and anoikis (Bachelder, R. E., Wendt, M. A., Fujita, N., Tsuruo, T., and Mercurio, A. M. (2001) J. Biol. Chem. 276, 34702-34707). In this study we showed that cytokine withdrawal resulted in Akt degradation by caspases as well. Furthermore, we demonstrated residue Asp-462 of Akt1 which is just upstream of the hydrophobic motif to be the primary cleavage site. The Akt1 mutant (D462N) that prevented caspase cleavage was more stable during factor withdrawal and enhanced cell survival. The Akt truncation mutant mimicking the caspase cleavage product lost its kinase activity and functioned as a dominant negative to promote cell death. Our results suggest that the balance between Akt and caspase activity controls cell survival. In particular, caspases are able to render Akt inactive and dominantly inhibit the Akt pathway by cleaving off the C-terminal hydrophobic motif. Consequently, the survival signal is quickly down-regulated to allow apoptosis to occur.     

Involvement of D1 dopamine receptors in the nicotine-induced noradrenaline release from hypothalamic and preoptic noradrenaline nerve terminal systems

Nicotine (4 × 2 mg/kg, i.p.) was given every 30 min for 2 h to male rats. Some rats were pretreated with the D1 dopamine (DA) receptor antagonist SCH 23390 (1 mg/kg, i.p.) or with the D2 DA receptor antagonist raclopride (1 mg/kg, i.p.), 5 min before nicotine treatment. Hypothalamic and preoptic catecholamine levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline nerve terminal systems.Nicotine treatment produced a depletion of catecholamine stores in noradrenaline and DA nerve terminals of the hypothalamus, the preoptic area and the median eminence, an action which was counteracted by SCH 23390 but not by raclopride.The results indicate that hypothalamic D1 DA receptors may regulate the sensitivity of the nicotinic cholinoceptors and increase their ability to release hypothalamic noradrenaline. A possible role of D1 DA receptor antagonists to reduce the ability of nicotine treatment to produce rapid increases in LH, prolactin and corticosterone secretion and tonic arousal is implicated.     

The role of the glutathione system in seizures induced by diphenyl diselenide in rat pups

The present study investigated the role of the glutathione system in seizures induced by diphenyl diselenide (PhSe)₂ (50 mg/kg) in rat pups (post natal day, 12–14). Reduced glutathione (GSH) (300 nmol/site; i.c.v.), administered 20 min before (PhSe)₂, abolished the appearance of seizures, protected against the inhibition of catalase and δ-aminolevulinic dehydratase (δ-ALA-D) activities and increased glutathione peroxidase (GPx) activity induced by (PhSe)₂. Administration of l-buthionine sulfoximine (BSO, a GSH-depleting compound) (3.2 μmol/site; i.c.v.) 24 h before (PhSe)₂ increased the percentage (42–100%) of rat pups which had seizure episodes, reduced the onset for the first convulsive episode. In addition, BSO increased thiobarbituric acid reactive species (TBARS) levels and decreased GSH content, catalase, δ-ALA-D and Na⁺, K⁺-ATPase activities. Treatment with sub effective doses of GSH (10 nmol/site) and d-2-amino-7-phosphonoheptanoic acid (AP-7, an antagonist of the glutamate site at the NMDA receptor; 5 mg/kg, i.p.) abolished the appearance of seizures induced by (PhSe)₂ in rat pups. Sub effective doses of GSH and kynurenic acid (an antagonist of strychnine-insensitive glycine site at the NMDA receptor; 40 mg/kg, i.p.) were also able in abolishing the appearance of seizures induced by (PhSe)₂. In conclusion, administration of GSH protected against seizure episodes induced by (PhSe)₂ in rat pups by reducing oxidative stress and, at least in part, by acting as an antagonist of glutamate and glycine modulatory sites in the NMDA receptor.     

The role of dopamine and opioid systems in the regulation of maternal behavior

This review describes in detail the different components and neuroanatomical basis of maternal behavior and also methodological approaches to investigation of parental reactions. The contributions of some endocrinal and neuromediator brain systems (in the first place, opioid and dopaminergic) to the regulation of maternal behavior are reported. The influences of ligands of opioid and dopamine receptors on the expressions of paternal reactions are analyzed especially. In concluding part the reasons of maternal depression and possibilities of this malfunction pharmacological correstion are discussed.     

The effect of etorphine on dopamine and noradrenaline concentrations in different central nervous system structures in the rat

The effect of etorphine on dopamine and noradrenaline concentrations in different central nervous system structures in the rat. Acta Physiol. Pol., 1977, 28 (6): 529-540. Intramuscular administration of etorphine in immobilizing doses (0.008 mg/kg) was followed by a rise in dopamine concentration in the examined motor structures of the central nervous system (striopallidum, pons, cerebellum, lumbosacral intumescence of the spinal cord). Only in the motor centres of the frontal cortex dropamine concentration was decreased. At the time etorphine decreased the concentration of noradrenaline in striopallidum and raised it in the other examined structures of the central nervous system. A correlation was found between the concentrations of both substances, especially in the frontal motor centres and striopallidum. Post etorphine accumulation of dopamine in the striopallidum (for 6.369 to 11.322 mcg/g of fresh tissue) with simultaneous inhibition of motor activity of the animals suggests that etorphine inhibits the release of dopamine from the presynaptic elements in the motor centres of the central nervous system in rats. This leads to a decreased dopamine action on its receptors. Some post etorphine behavioral changes (rigidity, spastic flexion, muscle tremor) support this hypothesis.