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Action of meprobamate on spinal monosynaptic reflexes and on inhibitory pathways.

Meprobamate was administered intravenously to spinal cats, in cumulative doses of 30 to 40 mg./kg. each. Initial doses may have a variable action on monosynaptic reflexes. At times some reflexes are depressed, while others are enhanced or unaffected. When dose levels of 100 mg./kg. or higher are reached, monosynaptic reflexes, both flexor and extensor, are depressed. Monosynaptic reflexes can be strongly depressed by meprobamate, their input-output relations often remaining unchanged. In such cases there is thus no change in the spatial summation requirements of those motoneurons remaining in the excitable zone. Inhibitory pathways, both direct and disynaptic, are highly resistant to the action of meprobamate. The drug does not distinguish between the direct and disynaptic pathways. It is suggested that meprobamate acts as a general depressant of excitatory synaptic transmission.

Animals↗

Effects of peripheral inputs from hindlimb on the monosynaptic reflex of motoneurons innervating tail muscles.

The effects of group II muscle (PBSt, GS) and cutaneous afferent (Sur, SPc, Tib) inputs from the hindlimb on the monosynaptic reflexes of motoneurons innervating tail muscles were studied in lower spinalized cats. Stimulation of the cutaneous nerves at the conditioning-test stimulus interval of about 10-20 ms facilitated and inhibited the monosynaptic reflexes of ipsilateral and contralateral tail muscles, respectively. The effects of the muscle nerve stimulation were not so prominent as those elicited by cutaneous nerve stimulation. The monosynaptic reflex was also inhibited by muscle nerve stimulation at 10-50 ms intervals. The effects of conditioning stimulation of the hindlimb peripheral nerves at short intervals were depressed or blocked by section of the ipsilateral lateral funiculus at S1 spinal segment. These findings show that the neuronal pathway from hindlimb afferents to tail muscle motoneurons passed the lateral funiculus of the spinal cord and modulates the motoneuronal activity of tail muscles.

Afferent Pathways↗

Monosynaptic reflex response of spinal motoneurons to graded afferent stimulation.

Monosynaptic reflex response of spinal motoneurons to graded afferent volleys has been studied in natural populations and in a representative sample of individual motoneurons. By analysis of input-response relations certain of the requirements for initiation of reflex discharge have been defined. Initation of motoneuron discharge by monosynaptic afferent excitatory volleys results from the development of transmitter potentiality among members of a pool. Transmitter potentiality is considered to have the following characteristics: 1. It is a function of the number of active excitatory synaptic knobs, the degree to which such knobs are aggregated on the motoneuron soma, and the intensity of action per knob. 2. It has an appreciable spatial decrement and rapid temporal decay. 3. While transmitter potentiality has considerable dependence on number of active excitatory knobs, proximity of such knobs is an important variable. Total activation of a discrete zone does not appear to be necessary for initiation of discharge. In addition to initiation of discharge, volleys in monosynaptic afferent excitatory fibers facilitate response otherwise engendered. Such facilitation depends upon the production of an increment in transmitter potentiality. Facilitator potentiality has the following characteristics: 1. It depends principally on number of active excitatory synaptic knobs and intensity of action per knob. 2. Facilitatory action may result from synchronous activity in knobs interspersed among aggregations of knobs otherwise activated, thus fulfilling spatial requirements for transmitter potentiality. Alternatively a residual facilitation may result from a generalized action. 3. Residual facilitation has a slow temporal decay in comparison with transmitter potentiality.

Motor Neurons↗

The modulation of the monosynaptic reflex by substance P in the hemisected spinal cord preparation of the rat and gerbil.

The effects of substance P and the selective neurokinin-1 receptor antagonist (+/-)-CP-96,345 have been compared on in vitro spinal cord preparations from the rat and the gerbil. Substance P produced a concentration-dependent depolarization of motoneurons recorded from ventral roots of both species. The EC50 values (microM mean +/- S.E.M.) obtained in rat (0.95 + 1.0/-0.49) and gerbil (0.47 + 0.26/-0.17) preparations were comparable. The mean maximal depolarization (mV mean +/- S.E.M.) evoked in rat (2.07 + 0.26/-0.25) was approximately two-fold greater than that evoked in gerbil (1.21 + 0.15/-0.14) preparations. In the rat substance P had a biphasic effect (depression followed by potentiation) on the short latency probably monosynaptic reflex evoked by electrical stimulation of a dorsal root. In gerbil preparations substance P produced only potentiation of the monosynaptic reflex. The EC50 values (microM) mean +/- S.E.M.) for this potentiating action in rat (0.97 + 0.75/-0.43) and gerbil (0.46 + 3.6/-0.4) preparations were similar. This potentiation demonstrates a positive modulation of an endogenous excitatory probably glutamatergic transmission by substance P in the ventral horn of the spinal cord. The depressant phase observed in rat preparations may be related to the relative immaturity of myelination in rat ventral root fibres compared to the gerbil. The selective neurokinin-1 antagonist (+/-)-CP-96,345 was one hundred-fold less potent as an antagonist of substance P-induced depolarizations in the rat (pA2 4.69 +/- 0.18, n = 7) than in the gerbil (pA2 6.79 +/- 0.16, n = 5) spinal cord. This finding suggests that (+/-)-CP-96,345 may not act solely at the neurokinin-1 recognition site. In conclusion this study demonstrates that substance P modulates the monosynaptic reflex in the spinal cord presumably via activation of neurokinin-1 receptors.

Action Potentials↗

The action of para-methoxyphenylethylamine (PMPEA) on monosynaptic reflex transmission in the cat.

1. The intravenous injection of para-methoxyphenylethylamine (PMPEA) into cats produces an increase in the size of the spinal cord monosynaptic reflex. The reflex elevation occurs within 30 s of drug administration, reaches a peak within 2 min, and lasts about 20 min.2. The action of PMPEA is similar for extensor (gastrocnemius-soleus) and flexor (posterior biceps-semitendinosus) monosynaptic reflexes.3. Repeated doses of PMPEA give comparable effects. The degree of monosynaptic reflex elevation is dose related.4. The action of PMPEA is antagonized by phenoxybenzamine and by methysergide or cyproheptadine. The combination of phenoxybenzamine with either of the latter is particularly effective in preventing the reflex facilitation by PMPEA.5. It is concluded that PMPEA has a central action on the spinal cord. It seems likely that monoaminergic synapses are involved.

Animals↗

[Modulation of spinal monosynaptic reflexes during rhythmical jaw movements and its central neural mechanisms].

The present study was carried out to investigate whether there was any modulation of the spinal monosynaptic reflexes during mastication in the healthy humans and urethane-anesthetized rabbits and to elucidate the central neural mechanisms responsible for the modulation in the urethane-anesthetized rabbits. 1. Human soleus H-reflex was significantly facilitated during the rhythmical jaw movements and rhythmical gum chewing. 2. There was no significant difference in the magnitude of the facilitation between the jaw-opening and -closing phases. 3. In the rabbits, monosynaptic reflex (MSR) volleys recorded from the tibial nerve (TIB) innervating the crural extensors and the common peroneal nerve (CP) innervating the crural flexors tonically increased in amplitude during the masticatory movements induced by either intraoral stimulation or repetitive stimulation of the cortical masticatory area (CMA). 4. Antidromic field potentials in the anterior horn of the lumbar cord evoked by the stimulation of TIB and CP increased during the CMA-induced actual and fictive mastication. 5. There was no significant change in the amplitude of the directly evoked antidromic potential in the primary afferents by intraspinal stimulation during the CMA-induced mastication compared with the resting state. It was concluded that (1) the MSR of the crural muscles undergoes a tonic non-reciprocal facilitation during mastication, (2) the stomatognathic afferents induced during mastication are not essential for the facilitation, and (3) an increase in the excitability of motoneurons is mainly involved in the facilitation of the MSR during mastication.

Adult↗

Spinal source for the synchronous fluctuations of bilateral monosynaptic reflexes in cats.

Successive stimuli of constant intensity applied to Ia afferents produce spinal monosynaptic reflexes (MSRs) of variable amplitude. We recorded simultaneous MSRs in the left and right L7 (or L6) ventral roots of anesthetized cats. We analyzed the cross-covariance (CCV) between the amplitudes of bilateral MSRs. Long-time series (5 to 8 h) of these bilateral MSRs exhibited transitory changes in their covariations (as measured by the zero-lag peak of their CCV), thus suggesting the existence of certain neural sources contributing to produce these changes. The aim of the present study was to show that spinal centers producing negative spontaneous cord dorsum potentials (nSCDPs) contribute to maintain correlations in the amplitude of bilateral MSRs. After spinal cord transection at the L1 segment, no significant changes were observed in the correlation between the amplitude of bilateral nSCDPs versus the amplitude of bilateral MSRs. However, this correlation, as well as the peak at zero lag in the CCV between bilateral MSRs and the CCV between bilateral nSCDPs, respectively, were abolished after a subsequent longitudinal bisection at the L1-S2 spinal segments. These results suggest that lumbar spinal neurons (bilaterally interconnected) contribute to maintain the synchronous fluctuations of bilateral MSRs.

Animals↗

Effects of stimulation of group I afferents from flexor muscles on heterosynaptic facilitation of monosynaptic reflexes produced by Ia and descending inputs: a test for presynaptic inhibition.

1. In the chloralose anesthetized cat, conditioning stimulation of group I flexor afferents depresses the monosynaptic potentials generated by Ia afferents in single spinal motoneurons or in populations of motoneurons without affecting the monosynaptic potentials produced by stimulation of descending fibers in the ipsilateral ventromedial fasciculus (VMF). 2. Heterosynaptic facilitation of monosynaptic reflexes was used to test changes in the presynaptic effectiveness of excitatory inputs with direct connections with motoneurons. We found that the heterosynaptic facilitation of Ia origin was reduced by conditioning stimulation of group I afferents from flexors, without affecting the heterosynaptic facilitation produced by stimulation of the VMF. 3. These results confirm and expand previous observations showing that the synaptic effectiveness of descending fibers synapsing with motoneurons is not subjected to a presynaptic control mechanism of the type acting on Ia fiber terminals, and provide further basis for the use of changes in heterosynaptic facilitation of monosynaptic reflexes of Ia origin as an estimate of changes in presynaptic inhibition of Ia fibers (Hultborn et al. 1987a).

Animals↗

Enhancement of recurrent inhibition of the spinal monosynaptic reflex by preceding stimulation of the medullary raphé in rats.

Recurrent inhibition of the spinal monosynaptic reflex (MSR) elicited by conditioning stimulation of the ventral root in anesthetized rats was weaker than both the recurrent inhibition of the disynaptic reflex and the inhibition of the MSR elicited by conditioning stimulation of the adjacent dorsal root. Among these 3 inhibitions, the recurrent inhibition of the MSR was enhanced to a markedly greater extent by a preceding stimulation of the medullary raphé nucleus than were the other inhibitions. The magnitude of the enhancement of the recurrent inhibition of MSR also was much greater when the medullary stimulation was delivered 20 ms prior to the ventral root activation, as compared with a 30-ms interval. Recurrent inhibition of the MSR was enhanced by intravenous injection of lysergic acid diethylamide (LSD); however, the enhanced effect on recurrent inhibition elicited by stimulation of the raphé nucleus was not attenuated by the drug. These results suggest that there is a non-serotonergic, descending pathway which is capable of modulating motor output solely by means of recurrent inhibition of the MSR.

Animals↗

Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats.

The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N-methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2-aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens.

Animals↗

Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. II. Determination of phospholipids at maximum of potentiation.

A monosynaptic reflex pathway was used to produce a post-tetanic potentiation (PTP). in ten experiments (cats) one side was tetanized (via N. gastrocnemius) whereas the other one was taken as control. Tissue was punched out of the ventral horn area of the spinal cord (segment height L7/S1) for the analysis of the phospholipid content. The results demonstrate that PTP significantly increases phosphatidyl-inositol in the potentiated alpha-motoneurone area. Phosphatidylserine showed a trend towards a decrease; sphingomyelin, phosphatidylcholine and phosphatidylethanolamine remained almost unchanged. The effect of a different tetanizing time on the phospholipid content is discussed as is the intention of the present experiments.

Action Potentials↗

[Descending modulation of monosynaptic reflexes after traumatic injury of the cat spinal cord].

Studies of the descending modulation of monosynaptic reflex responses have revealed that electrical stimulation of dorsolateral, ventrolateral and ventral funiculi in C2 facilitated and suppressed test responses of intact animals, but evoked only suppression of spinal reflexes after injury of the spinal cord. The obtained data have shown that descending pathways which transmit facilitatory influences are more vulnerable to injury of the spinal cord.

Animals↗