The effect of DOPA on the reciprocal inhibition of the innervation centers of antagonistic muscles in newborn rat pups]

In experiments on 5--7- and 16-day rat puppies with acute lesion of the spinal cord, by means of monosynaptic tests, studies have been made of the effect of DOPA on reciprocal inhibition of antagonist muscles. Test stimuli were applied to n. tibialis, conditioned ones--to n. peroneus. It was shown that the pattern of the effects depends on the action of the drug on the magnitude of the initial monosynaptic reflex used as a test. It the latter was initially inhibited, the conditioned stimulation resulted within the first 1-8 msec not in the development of postsynaptic inhibition, but in evident facilitation, which was longer in 5--7-day animals. The level of presynaptic inhibition was somewhat lower than the initial one, but exhibited longer duration. In case of facilitation of a control test after DOPA injection, configuration of reciprocal inhibition curves did not significantly differ from that obtained before administration of the drug.     

The effect of L-DOPA on potentials of the dorsal surface of the spinal cord evoked by the stimulation of primary afferents in newborn rat pups

In experiments on 5-30-day rat puppies, studies have been made of the effect of L-DOPA (100 mg/kg, intraperitoneally) on the activity of interneurones of the dorsal horn of the spinal cord as revealed from the parameters of potentials of the dorsal surface of the spinal cord. The specific pattern of reaction in 5-day animals is manifested in a succession of inhibitory inhibition and increase in the activity of neurones monosynaptically activated by low-threshold afferents. Both the amplitude and duration of polysynaptic components of the potentials of the dorsal surface are rather high. From the 7th day, deep and stable inhibition is observed which is accompanied by a decrease in the amplitude of all components of the potential of the dorsal surface. At later stages of ontogenesis, a decrease is observed in the inhibitory effect of L-DOPA on the activity of interneurones which monosynaptically contact with low- and especially high-threshold afferents; in contrast to earlier stages, but similar to adult animals, evident inhibition was revealed in the activity of interneurones which have polysynaptic contacts with high-threshold afferents and afferents of flexor reflex. Thus, within the first weeks of postnatal life, basic qualitative changes are observed in the pattern of the reaction of interneurones of the dorsal horn to exogenic catecholamines.     

Effect of peripheral heating and cooling on spinal reflex activity

The effects of heating and cooling the skin of the thigh and leg on the character of changes in monosynaptic and polysynaptic reflexes and of the first negative wave (N_`) of the dorsal cord potential was studied in acute experiments on lightly anesthetized cats. During cooling of the skin the amplitude of the monosynaptic reflex and N₁-wave was increased while the polysynaptic reflex was inhibited; during heating the amplitude of the monosynaptic reflex and N₁-wave was reduced while the polysynaptic reflex was increased. After de-efferentation the cooling effect was reduced, and after division of the spinal cord responses to cooling of the skin were considerably inhibited. The mechanism of the selective action of cooling and heating of the skin on monosynaptic and polysynaptic reflexes are discussed.Institute of Physiology, Academy of Sciences of the Kazakh SSR, Alma-Ata. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 181–185, March–April, 1973.     

Short and long latent effects of 15-hydroxyeicosatetraenoic acid on the extinction of the acetylcholine-induced inward current in neurons of the Helix lucorum]

The impact of a non-cyclized arachidonic acid derivative 15S-hydroxy-5Z, 8Z, 11Z, 13E-eicosatetraenoic acid (15-HETE) upon the dynamics of the inward current extinction, caused by repeated ion-tophoretic acetylcholine applications on the soma, was studied through a double electrode voltage clamp technique on the Helix lucorum identified neurons RPa3 and LPa3. The extracellular effect of 15-HETE (4-16 microM) was found to have a two phase influence on the inward current extinction, depending on the time of exposure to the compound. The short-latent effect (up to 60-80 min) displays itself as an extinction decrease, whereas the long-latent effect (after 60-80 min) - as an enhanced extinction. The effects caused by 15-HETE are irreversible. The short-latent one was probably due to the earlier described inhibition of 5- and 12-lipoxygenase enzymes by 15-HETE while the long-latent one - due to its intrinsic function.     

The expiration reflex during ontogenesis in the rat.

The authors studied the elicitability of the expiration and aspiration reflex and of the respiratory reaction from the tracheobronchial area in 131 anaesthetized rats (aged 1-15 days, adult and biologically old). They found that the expiration reflex could be elicited, in the rat, from the first day of life, at a time when other respiratory reflexes were not yet stable. In young rats, the expiration reflex was often followed by a cough reaction which was absent in adult animals. The findings indicate that the expiration reflex is one of the most important respiratory reflexes of the early postnatal period in the rat, because the aspiration reflex and the respiratory reaction from the bronchi were not stable until the 15th day of life. In biological old rats, the expiration reflex is less frequently elicited and its intensity attains about half the value found in adult animals. The aspiration reflex and the respiratory reaction from the bronchi are likewise less readily elicited than in adult animals, but when the intensity of their maximum expiratory effort is increased, it is far greater.     

Facilitation between extensor carpi radialis and pronator teres in humans: A study using a post-stimulus time histogram method

Group I muscle afferents modulate the excitability of motor neurons through excitatory and inhibitory spinal reflexes. Spinal reflex relationships between various muscle pairs are well described in experimental animals but not in the human upper limb, which exhibits a fine control of movement. In the present study, spinal reflexes between the extensor carpi radialis (ECR) and pronator teres (PT) muscles were examined in healthy human subjects using a post-stimulus time histogram method. Electrical stimulation of low-threshold afferents of ECR nerves increased the motor neuron excitability in 31 of 76 PT motor units (MUs) in all eight subjects tested, while stimulation of low-threshold afferents of PT nerves increased the motor neuron excitability in 36 of 102 ECR MUs in all 10 subjects. The estimated central synaptic delay was almost equivalent to that of homonymous facilitation. Mechanical stimulation (MS) of ECR facilitated 16 of 30 PT MUs in all five subjects tested, while MS of PT facilitated 17 of 30 ECR MUs in all six subjects. These results suggest excitatory reflex (facilitation) between PT and ECR. Group I afferents should mediate the facilitation through a monosynaptic path.     

Post-tetanic potentiation of polysynaptic reflexes of the spinal cord

The phenomenon of post-tetanic potentiation has been studied in the cat spinal cord with particular reference to polysynaptic responses. Following tetanization of dorsal roots, these reflexes show an increased response, as measured in terms of their voltage-time area, with a predominant change in the earlier reflex pathways. Both of these changes in the reflex discharge have a time course of 15 to 25 seconds. Post-tetanic potentiation is also observed in response to stimulation of a dorsal rootlet following tetanization of another rootlet in the same or in a neighboring segment. This effect can be explained by post-tetanic changes in the terminals of secondary, and possibly higher order, internuncial cells, essentially similar to those changes in the primary afferent terminals which give rise to potentiation of the monosynaptic reflex.     

The effect of low-level prenatal X-irradiation on postnatal development in the Wistar rat

The objective of this investigation was to determine the effect of low-dose prenatal X-irradiation on postnatal growth and neurobehavioral development, and whether alterations would manifest at dosages lower than those which produce anatomic malformations from exposure at the most sensitive period of organogenesis. Ninety-eight Wistar strain rats were exposed to 0.1, 0.2, or 0.4 Gy X-radiation of were sham irradiated on the 9th or 17th day of gestation. A conventional teratologic evaluation was completed on half of the animals (572 fetuses). The age of appearance of four physiologic markers and of acquisition of six reflexes was observed in 372 offspring. Exposure during early organogenesis at these levels had no effect on any of these parameters. Prenatal exposure to X-radiation on the 17th day of gestation at dosage levels greater than 0.1 Gy resulted in alterations in the appearance of three postnatal neurophysiologic parameters. Growth retardation throughout the postpartum period also was observed in the offspring. The induction of developmental and reflex alterations had a comparable threshold to the known threshold for anatomic malformations on the 9th day. These results indicate that all of the parameters studied had thresholds either at or above 0.2 Gy acute radiation, and that the postpartum developmental and reflex acquisition measures were not more sensitive indicators of exposure to X-radiation than growth parameters.     

Posttetanic changes in the afferent and efferent activity of monosynaptic reflex in kittens

Both the afferent volleys from the dorsal root and the monosynaptic reflex discharges from the corresponding ventral root were recorded with hook electrodes during stimulation of the nerves innervating the triceps surae muscles. The effects of conditioning high frequency tetanus on the magnitudes of these afferents and reflex volleys were examined in kittens of postnatal age 1-90 days and in adult cats. In young kittens under barbiturate anaesthesia, large-amplitude monosynaptic reflex discharge can be evoked without prior conditioning. The amplitude of this reflex discharge decreased with increasing age of the animal. Application of conditioning tetanic stimuli to the muscle nerves resulted in posttetanic depression followed by posttetanic potentiation of the monosynaptic reflex. The magnitude of posttetanic depression was much higher than that of potentiation in the first postnatal week. As the age increased, the magnitude of depression decreased while the magnitude of potentiation increased. The afferent volley showed a considerable posttetanic potentiation in older kittens and cats. No significant potentiation or depression was observed in the younger animals. Possible mechanisms contributing to posttetanic depression and potentiation are discussed.     

The effects of cold-induced muscle spindle secondary activity on monosynaptic and stretch reflexes in the decerebrate cat.

The effects of muscle spindle secondary ending activity on the stretch reflex were studied in unanesthetized decerebrate cats. Activation of secondary endings was accomplished by reducing the muscle temperature. This has been shown to cause a sustained asynchronous discharge from secondary endings. Cooling of the medial gastrocnemius or lateral gastrocnemius-soleus muscles caused an increase in the phasic and tonic components of their stretch reflexes. Cooling of the relaxed medial gastrocnemius muscle caused similar increases in the components of the stretch reflex of the synergistic lateral gastrocnemius-soleus muscle and an increase in its monosynaptic reflex. It was concluded that the facilitatory autogenetic and synergistic effects of muscle cooling on the stretch and monosynaptic reflexes were brought about by activity in group II afferents from muscle spindle secondary endings and could not be ascribed to any other type of muscle receptor. These results support the concept of an excitatory role for the secondary endings of the muscle spindle in the stretch reflex of the decerebrate cat.     

Reflex mechanisms of fore-hindlimb relations demonstrable in lumbar flexor centers of the cat spinal cord

The dynamics of interaction between segmental, propriospinal, and spino-bulbo-spinal components of reflex responses of lumbar flexor centers was investigated during activation of forelimb and hindlimb afferents in cats. The monosynaptic flexor reflex to activation of hindlimb afferents is facilitated up to 300% when it coincides in time with the reflex discharge evoked by activation of forelimb afferents, and it remains increased up to 120–140% for 40–50 msec during the aftereffect of such activation. Polysynaptic flexor reflexes of segmental, propriospinal, and spino-bulbo-spinal origin have both facilitatory and inhibitory effects on each other. Facilitation is observed only while the interacting responses coincide in time, inhibition when they do not coincide. Three type of inhibitory effects with durations of 7–15, 40–150, and 300–500 msec are observed. The possible neuronal mechanisms of interaction between these reflexes and their role in functional relations between the fore- and hindlimbs are discussed.     

Inhibitory effect of dopamine on the transmission of excitation in isolated rat spinal cord

The effects of dopamine on ventral root potential produced by a single supramaximal dorsal root stimulation of the dorsal root was investigated during experiments on isolated superfused spinal cord segments from 10–16-day old rats. A reciprocal dose-dependent inhibition of the mono- and polysynaptic components of reflex response was also observed. Minimum effective concentration was 1×10^–8 M dopamine. Extent of reflex response increased in step with dopamine concentration, so that the amplitude of the monosynaptic component of ventral root potential was decreased by 20% and 87% of baseline level by the action of 10^–4 and 10^–3 M dopamine respectively on the cord. The amplitude of the polysynaptic component was thereby decreased by an average of 18% and 87%. Findings indicate that dopaminergic brainstem-spinal pathways contribute to the governing of impulse transmission in the segmental reflex arcs. Inhibition of dopaminergic synaptic transmission probably underlies the increase in latency already described in the literature, as well as the increase observed in the threshold of reflex motor response to nociceptive action following either stimulation of the dopaminergic brainstem structures or intravenous administration of dopamine agonists.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 616–621, September–October, 1986.     

The late prolonged motor discharges during stimulation of the segmentary afferents in rat pups: the effect of L-DOPA

In experiments on 5-30-day rat puppies, under slight urethane narcosis, studies have been made on the late prolonged discharges in extensor muscles evoked by stimulation of contralateral tibial nerve before and after injection of DOPA. Within the first 16 days, the drug completely abolished or significantly reduced late discharges, increasing the spontaneous motor activity. Beginning from the 16th day, periods of potentiation of late discharges were observed. The data obtained are discussed in relation to the development of mechanisms of control of the activity of spinal generators which are responsible for late discharges and spontaneous motor activity.     

Effects of Podophyllum hexandrum on radiation induced delay of postnatal appearance of reflexes and physiological markers in rats irradiated in utero.

Effect of 2.0 Gy gamma-dose delivered to rats in utero on 17th day of gestation was studied to monitor the radiation induced retardation of neurophysiological development in postnatal young ones. Rhizome of Podophyllum hexandrum which has been well documented for mitigating radiation injuries in adult mice was attempted for modifying radiation damage. Rats were observed from postnatal day 1 to 25 for the age of the appearance of physiological markers (pinna detachment, inscisor's eruption, eye opening) and acquisition of reflexes (surface righting, visual placing, reflex suspension, negative geotaxis). In irradiated groups there was a significant weight reduction in mother rats and offsprings throughout the experimental period. There was radiation-induced delay in the appearance of pinna detachment but not in eye opening and inscisor's eruption. Appearance of the reflexes were also delayed due to irradiation. Preirradiation administration of the extract of Podophyllum hexandrum (i.p., 200 mg/kg/b.w.) mitigated radiation induced postnatal physiological alterations. These studies have implications in protection against damage (in utero) due to planned radiation exposure.     

Electrophysiological and pharmacological analysis of L-dopa-induced dyskinesia and tardive dyskinesia (author's transl)

Electrophysiological and pharmacological analysis of L-Dopa-induced dyskinesia and tardive dyskinesia (L.DD) due to neuroleptics was performed on 12 patients with Parkinson's disease and on 12 others with psychotic diseases. This analysis included the examination of spinal reflexes, monosynaptic H reflex, polysynaptic cutaneous reflex of the lower limb, muscular responses to passive movement [stretch reflex and shortening reaction (SR)] and the study of the motor response to a dopaminergic stimulus (I.V. injection of Piribedil (PBD), a dopamine agonist). There was no difference in EMG activity between L.DD and TD. Three EMG patterns can be distinguished: anarchic discharge pattern (ADA), tonic grouping discharge pattern (AST) and rhythmic burst pattern (ABR). PBD effects indicate a possible relationship between the EMG patterns and the sensitivity level of the motor dopamine receptors. During L-Dopa dyskinesia and tardive dyskinesia, the same changes in spinal reflexes were observed. Muscle tone tested by muscular responses to passive movement (shortening and myotatic reaction) was normal. Monosynaptic excitability explored by H/M ratio was within the normal range. In contrast, the polysynaptic nociceptive reflex was increased in every case. In Parkinsonian patients with L-Dopa dyskinesia, this pattern of the spinal reflexes was significantly different in comparison to the rigid phase. Intravenous infusion of PBD suppressed tremor and provoked the occurrence of dyskinetic activity in Parkinsonian patients with L-Dopa dyskinesia during the rigid phase. During the dyskinetic phase, as in tardive dyskinesia, PBD increases these phenomena and changes EMG activity in rhythmic pattern. It is suggested that L-Dopa dyskinesia and tardive dyskinesia can be determined by testing EMG activity, spinal reflexes and dopaminergic reactivity. There is evidence to suggest that the various types of involuntary abnormal movement represent a single entity, and that dopamine receptor supersensitivity may be involved.     

The effect of intraspinal microinjection of dopamine on the C-fiber reflex in the acute decerebrate spinal cat.

Dopamine microinjection (10 μg) into the ventral spinal cord gray matter of the L₇ segment of the spinal cord facilitated the C-fiber reflex; however, facilitation occurred after a latency of 15 min. In contrast norepinephrine (10 μg) microinjections facilitated the C-fiber reflex after a shorter latency (2 min). Treatment of the cat with a dopamine ß-hydroxylase inhibitor prevented the facilitatory effect of dopamine. These observations indicate that microinjected dopamine facilitates C-fiber reflexes by serving as a precursor for norepinephrine.     

Effects of Local and Remote Muscle Pain on Stretch ReflexActivities in the Elbow Joint Flexors and Extensors of Unanesthetized Cats

In experiments on unanesthetized cats, we compared the effects of experimentally induced pain in the m. biceps brachii or in the neck muscles on EMG activity of the flexors and extensors of the elbow joint (mm. biceps et triceps brachii, respectively) evoked by a passive extension-flexion of the above joint. Muscle pain was induced by injections of 0.5 ml of a hypertonic (7%) NaCl solution into the above-mentioned muscles. In the case of pain in the biceps, i.e., in the muscle directly involved in realization of the reflex, we observed an increase in the amplitude and significant shortening of the latency of EMG responses of this muscle. The amplitude of a short-latency (supposedly monosynaptic) component of the biceps reflex (М1 response) increased by 65%, while an increment of the latter (supposedly polysynaptic) М2 component was 117%. When pain was induced in anatomically remote neck muscles, the stretch reflex in the biceps was considerably suppressed. The maximum amplitudes of the М1 and М2 components decreased by 25 and 30%, respectively, but the latencies of these components decreased significantly, similarly to what was observed in the case of induction of experimental pain in the biceps. Under both conditions of experimental pain, changes in the parameters of EMG responses of the forearm extensor (m. triceps brachii) demonstrated similarity with those of the biceps responses. The maximum effect of pain induction was observed within the first 5 min after injections of the hypertonic solution; full recovery of the stretch reflex parameters was observed on the 20th to 30th min. We conclude that the effects of pain induction on the reflex under study are not generalized. They depend on the site of such induction with respect to the muscle where the stretch reflex is elicited. Unidirectional effects of both types of pain on the antagonist muscles allow us to suppose that modulation of the reflex reactions upon pain induction is mediated by influences from the supraspinal CNS structures. Induction of pain in the biceps increased the amplitude of EMG manifestations of the stretch reflex, while such induction in the neck muscles decreased such responses; nonetheless, in both cases the latency of the reflexes decreased. This fact allows us to believe that the sensitivity of muscle spindles increased under both conditions of the pain influence.     

The effects of prenatal X irradiation on the appearance of reflexes and physiologic markers in the neonatal rat

Seventy pregnant adult Wistar strain rats were randomly assigned to 1 of 12 exposure groups; 9th or 17th day irradiation at the 0-, 0.1-, 0.2-, 0.4-, 0.6-, or 0.8-Gy dosage level. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter. A total of 508 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). A dose-response relationship for alterations in reflex acquisition and physiologic marker appearance was observed due to exposure above 0.2 Gy on the 17th day of gestation. Therefore, 0.2 to 0.4-Gy exposure may represent a threshold range for exposure on the 17th day using these postnatal parameters.     

Effect of helium-neon laser on the microcirculation in blood vessels of the rat pia mater

The sensitivity of rat's microvessels of microcirculatory bed of brain's pia matter was studied by helium-neon laser radiation. Changes in the reactivity by the microscopy findings were studied on the 7, 30, 45, 60, 90th days of animals postnatal development. Laser radiation was used during 30 min. Local changes in all components of the microcirculatory bed were fixed. It is mentioned that in adult rat the expressiveness of arteriole's local widening reaction in the radiated place reduces, but the degree of the reduction is below or over the radiated place, on the contrary, increases. The arteriole diameter in 30-day old rats increases to 59% in comparison to the initial level, and 90th day old animals--to 16%. The degree of reaction's expressiveness depends upon the microvessel diameter and the animal's age.     

Conditional Reflex Reaction of the Passive Avoidance in Female and Male Rats Exposed to Hypoxia at Different Terms of Prenatal Development

Elaboration of the conditional reflex reaction of passive avoidance was studied in the 42–46-day old offsprings of two groups of female rats: intact (control) and exposed to action of hypoxia at the 13th, 16th or 19th day of pregnancy. The parameter of learning was the time of stay of the rats in a dark camera, in which they obtained an electroshock. It is shown that the prenatal hypoxia has different effect on the ability to elaborate the conditional reflex reaction of passive avoidance in female and male rats. By this parameter, no differences were revealed in the male group between the control and the animals exposed to hypoxia at different terms of intrauterine development. In female exposed to hypoxia at the 19th day of gestation, it was not possible to elaborate the conditional reflex reaction of passive avoidance. In females exposed to hypoxia at the 13th day of gestation the parameters of learning were lower, whereas in the females exposed to hypoxia at the 16th gestation day they were higher than in control animals.