Depression Of Monosynaptic Reflex Research Articles

Involvement of 5-hydroxytryptaminergic transmission for the Mesobuthus tamulus venom-induced depression of spinal reflexes in neonatal rat in vitro

Mesobuthus tamulus (MBT) venom is shown to depress the spinal reflexes through a mechanism unrelated to the NMDA receptors. 5-Hydroxytryptamine (5-HT) is another excitatory transmitter in the spinal cord therefore, the present study was undertaken to examine the involvement of 5-HT in the venom-induced depression of reflexes. The experiments were performed on isolated hemisected spinal cords from 4 to 6-day-old rats. Stimulation of a dorsal root with supramaximal strength evoked monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials in the corresponding segmental ventral root. MBT venom (0.3 μg/ml) depressed the spinal reflexes in a time-dependent manner and the maximal depression was seen at 10 min. The time to produce 50% depression (T-50) of MSR and PSR was 8.1 ± 1.41 and 6.8 ± 0.5 min, respectively. Pretreatment with pindolol (1 μM; 5-HT 1A/1B receptor antagonist) blocked the reflexes up to 15 min. On the other hand, ketanserin (10 μM; 5-HT 2A/2C receptor antagonist) or ondansetron (0.1 μM; 5-HT 3 receptor antagonist) blocked the venom-induced depression of MSR and PSR during entire exposure time (30 min). The 5-HT concentration of the cords exposed to venom (1.6 ± 0.04 μg/g tissue) was significantly greater than the control group (0.98 ± 0.08 μg/g tissue). The results indicate that venom-induced depression of spinal reflexes is mediated via 5-HTergic transmission involving 5-HT 1A/1B, 5-HT 2A/2C and 5-HT 3 receptors.

Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic reflex via 5-HT 1D receptors

In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT 1B receptors mediate the monosynaptic reflex depression induced by exogenously applied 5-HT that was formed from the precursor l-5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by dl-p-chloroamphetamine, on spinal reflexes. dl-p-Chloroamphetamine depressed the monosynaptic reflex and increased the polysynaptic reflex. The depletion of 5-HT abolished the monosynaptic reflex depression, but the increase in polysynaptic reflexes was maintained, suggesting that endogenous 5-HT released by dl-p-chloroamphetamine mediates depression of the monosynaptic reflex in the spinal cord. The depression of the monosynaptic reflex was antagonized by GR127935 ( N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT 1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT 1D receptor antagonist) but not by isamoltane (5-HT 1B receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses monosynaptic reflex transmission via 5-HT 1D receptors.

Involvement of the GABAergic system for Ptychodiscus brevis toxin-induced depression of synaptic transmission elicited in isolated spinal cord from neonatal rats

The involvement of inhibitory transmitters for Ptychodiscus brevis toxin (PbTx)-induced depression of spinal synaptic transmission in neonatal rats was investigated. Stimulation of a dorsal root evoked monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root. The PbTx depressed the reflexes in a concentration-dependent manner and the depression was blocked by GABA A antagonist, bicuculline (1 μM). GABA also produced depression of the reflexes in a concentration-dependent manner. Simultaneous application of submaximal concentrations of PbTx (28 μM) and GABA (30 μM) enhanced the depression (>75%). In contrast, PbTx alone (28 μM) depressed the MSR and the PSR by 33 and 47%, respectively, and GABA (30 μM) alone depressed the reflexes by 30%. The N-methyl- d-aspartate receptor antagonist, dl-2-amino-5-phosphono-pentanoic acid (10 μM), blocked the PbTx-induced depression of MSR and also the enhancement of GABA response by PbTx. A glycine receptor antagonist, strychnine (1 μM), failed to block the depression by the toxin up to 28 μM; however, the depression was attenuated significantly at 84 μM of the toxin. The results indicate that PbTx depressed the spinal reflexes via GABA A receptors. Furthermore, the potentiation of GABAergic action by PbTx requires the N-methyl- d-aspartate dependent mechanism.

Relative potency of synthetic analogs of Ptychodiscus brevis toxin in depressing synaptic transmission evoked in neonatal rat spinal cord in vitro

Effects of Ptychodiscus brevis toxin (PbTx) analogs on the spinal synaptic transmission in neonatal rats in vitro were evaluated. PbTx 1/PbTx 2 had aromatic groups and PbTx 3/PbTx 4 had aliphatic groups. All the analogs depressed monosynaptic reflex (MSR) and polysynaptic reflex (PSR) in a concentration-dependent manner. The maximal depression of MSR (75% from initial) and PSR (96%) was at 84 μM for PbTx 1. Concentration to produce 25% inhibition from initial (IC25) by PbTx 1 for MSR and PSR was ⩽2.8 μM. The maximal depression of MSR (80%) was at 96 μM and PSR (100%) was at 32 μM by PbTx 2. IC25 for MSR and PSR were 5.5 μM and <3.2 μM, respectively. PbTx 3 decreased MSR by 25% maximally (=IC25) at 36 μM. The depression of PSR fluctuated and was maximal (75%) at 108 μM and IC25 was 6.2 μM. PbTx 4 depressed MSR and PSR at the maximum of 35% at 32 μM and IC25 for MSR was 8.3 μM and for PSR was 35 μM. Rank order of potency of toxins for depressing MSR was PbTx 1>PbTx 2≫PbTx 4>PbTx 3; and for PSR it was PbTx 2>PbTx 1>PbTx 3≫PbTx 4. Results indicate that the toxins having aromatic groups exhibited greater neurotoxicity.

No involvement of 5-HT 7 or 5-HT 1D receptors in the ( R)-8-OH-DPAT-induced depression of the monosynaptic reflex in spinalized rats

( R)-8-Hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT) depressed the monosynaptic reflex. This effect was not antagonized by 5-HT 1A receptor antagonists. We examined whether 5-HT 1D and 5-HT 7 receptors are involved in ( R)-8-OH-DPAT-induced inhibition of the monosynaptic reflex in spinalized rats. Pretreatment with methiothepin and mesulergine, but not clozapine, inhibited ( R)-8-OH-DPAT-induced monosynaptic reflex depression. Pretreatment with 2 a-(4-phenyl-1,2,3,6-tetrahydropyridal)butyl)-2 a,3,4,5-tetrahydrobenzo[ c, d]indol-2(1 H)-one (DR4004) and ( R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrolidine (SB-269970), new selective 5-HT 7 receptors antagonists, and N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide (GR127935), a selective 5-HT 1D receptor antagonist, had no effect on ( R)-8-OH-DPAT-induced depression. These results suggested that 5-HT 7 and 5-HT 1D receptors are not involved in ( R)-8-OH-DPAT-induced monosynaptic reflex depression.

Presynaptic inhibition in humans: A comparison between normal and spastic patients

During the last 40 years, several studies in man have been devoted to the pathophysiological mechanisms underlying spasticity. Spasticity is characterised by a velocity dependent increase in muscle tone. Many spinal pathways control stretch reflex excitability and a malfunction in any one of them could theoretically produce the exaggeration of the stretch reflex. Delwaide showed that the vibration-induced inhibition of Ia fibres is reduced in spastic patients. However, the relation between a decrease in presynaptic Ia inhibition and the pathophysiology of spasticity has been recently questioned since it was argued that homosynaptic depression (or post-activation depression) also contributes to the vibratory-induced depression of monosynaptic reflexes. This paper is thus devoted to a review of the methods recently developed to study selectively presynaptic Ia inhibition in man and to a reevaluation of the relations between modifications in presynaptic Ia inhibition and spasticity in hemiplegic and spinal spastic patients.

Differential effects of ( R)- and ( S)-8-hydroxy-2-(di- n-propylamino)tetralin on the monosynaptic spinal reflex in rats

We examined the effects of ( R)- and ( S)-8-hydroxy-2-(di- n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the monosynaptic spinal reflex in rats. In intact rats, ( R)-8-OH-DPAT (10 μg/kg, i.v.) enhanced the amplitude of the monosynaptic reflex, whereas at 100 μg/kg, it reduced the amplitude. ( S)-8-OH-DPAT enhanced the monosynaptic reflex dose-dependently. In spinalized rats, ( R)-8-OH-DPAT produced dose-dependent inhibition, but the ( S)-enantiomer did not affect the monosynaptic reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited ( R)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of ( R)-8-OH-DPAT. These pretreatment regimens had no effect on the monosynaptic reflex depression produced by the ( R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited ( S)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT 1A receptors and the descending serotonergic system are involved in the stimulatory effect of ( R)-8-OH-DPAT on the monosynaptic reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via α 1-adrenoceptors, are involved in the effect of the ( S)-enantiomer on this reflex.

Diisopropylfluorophosphate-induced depression of segmental monosynaptic transmission in neonatal rat spinal cord is also mediated by increased axonal activity

Involvement of dorsal and ventral root activity for the depressant action of diisopropylfluorophosphate (DFP) on synaptic transmission was examined using in vitro spinal cord/root preparations. Superfusion of DFP produced a dose-dependent depression of monosynaptic reflex (MSR) and maximal depression of about 80% occurred at 1000 μM. The concentration to produce 50% of the maximal inhibition was about 100 μM of DFP. The DFP (100 μM)-induced depression of MSR was reversed by atropine (0.5 μM) but not by mecamylamine (0.5 μM). Contrary to the action on MSR, DFP potentiated the ventral root potential and 1st peak of dorsal root potential. The maximal potentiation was about 25% of control in both the root potentials at 100 μM of DFP. However, the second peak of dorsal root potential was slightly depressed (10–20% of control) by DFP (1–1000 μM). Further, the cords treated with DFP (100 μM) showed significant decrease in the cholinesterase (ChE) activity (27% of control). Results suggest that the DFP-induced depression was mediated at least by two different mechanisms, one through the inhibition of ChE activity and the other through the activation axonal activity having inhibitory inputs to the segmental synaptic transmission. These inputs mediate their action through muscarinic receptors.

The influence of muscle spindle discharge on the human H reflex and the monosynaptic reflex in the cat.

1. Experiments were carried out to test the effect of changes in spindle resting discharge on the size of monosynaptic reflexes in the cat and on the H reflex in humans. Resting discharge was altered by contracting the triceps surae muscle at longer (hold-long) or shorter (hold-short) lengths than that at which the reflex was tested. 2. The reflex in the cat was larger after hold-long than after hold-short conditioning, and the difference, after an initial decline, was well maintained. For the human H reflex a similar pattern was observed except that 15 s after muscle conditioning the difference in reflex size had disappeared. 3. Monosynaptic reflex depression immediately after hold-long conditioning, when most of the muscle spindles are silent, was attributed to the high level of spindle discharge during the immediately preceding hold-long period. The time course of this inhibition was too long to be accounted for by presynaptic inhibition. 4. In the cat heteronymous muscle conditioning was used to test whether presynaptic inhibition could be responsible for reflex depression using the synergist muscle pair lateral gastrocnemius-soleus and medial gastrocnemius. Conditioning one of the pair did not affect the reflex in the other, the opposite result to that expected with presynaptic inhibition. A similar experiment in which the triceps H reflex in human subjects was facilitated by a quadriceps volley gave the same result. 5. Thus this study presents evidence that monosynaptic reflexes are depressed by the on-going discharge of muscle spindles in the homonymous muscle, but that this depression does not appear to involve "classical' presynaptic inhibition.

Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems

The centrally acting muscle relaxatn cyclobenzaprine was thought to be an α 2-adrenoceptor agoinst that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the α 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT 2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by dl- p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggests that cyclobenzaprine is a 5-HT 2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

1. The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and R(+)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and also by the selective 5-HT1D agonists, sumatriptan and N-methyl-3-(1-methyl-1-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548). 2. Ketanserin (1 microM) and methiothepin (1 microM) reduced the duration of depressions elicited by 5-CT, but not those produced by 5-HT, sumatriptan, GR 85548, methysergide or 8-OH-DPAT. 3. The IC50 for MSR depression by 5-CT was 3.6, 2.1-6.2 nM (n = 4), by sumatriptan was 15.2, 12.9-18.0 nM (n = 32), by GR 85548 was 18.4, 11.7-29.1 nM (n = 12), by methysergide was 29.8, 10.2-87.1 nM (n = 4) and by 8-OH-DPAT was 0.21, 0.11-0.43 microM (n = 3) (geometric means and 95% confidence limits). 4. Ketanserin (0.1 or 1 microM) antagonized competitively responses to sumatriptan (apparent pA2 7.8 +/- 0.1, n = 5), GR 85548 (apparent pA2 7.6, unpaired data, n = 5), methysergide (apparent pA2 7.9 +/- 0.12, n = 4) and 8-OH-DPAT (apparent pA2 8.3 +/- 0.1, n = 3). Concentration-response curves to 5-CT showed a smaller, parallel shift to the right (apparent pA2 6.8 +/- 0.1, n = 4), but responses to 5-HT were unaffected by ketanserin (1 microM) (n = 4). 5. Methiothepin (1 microM) antagonized competitively responses to GR 85548 (apparent pA2 7.7, unpaired data, n = 5). 6. Mianserin (0.3 microM), a concentration sufficient to cause substantial block of 5-HT2C-mediated responses but have only a small effect on 5-HT1D-mediated actions, caused a small, non-parallel shift of the concentration-response curve to sumatriptan. 7. Depression of the MSR by sumatriptan was not blocked by (+/-)-cyanopindolol (0.1 microM), (+/-)-propranolol (0.5 or 1 microM) or spiroxatrine (0.1 microM), and depression of MSR by 8-OH-DPAT was not blocked by spiroxatrine (0.1 microM). (+/-)-Cyanopindolol (0.1 and 1 microM) itself induced a slow depression of the MSR. 8. The novel 5-HT1D antagonist, N-[4-methyl-1-piperazinyl) phenyl]2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide (GR 127935, 30 nM to 1 microM) caused a concentration-related depression of the reflex (up to 50%) usually slow in onset. Neither with these concentrations nor with concentrations in the range 1-3 nM was there any unequivocal blockade of responses to sumatriptan. 9. It is concluded that sumatriptan, GR 85548, methysergide and 8-OH-DPAT depress the MSR in the neonate rat spinal cord via ketanserin-sensitive receptors, which have some similarities to 5-HT1D alpha receptors but which are not blocked by GR 127935. 5-HT released by tryptaminergic pathways may act via the same receptors to depress the MSR. 5-HT applied to the cord probably acts via a different, possibly novel 5-HT receptor to depress the MSR.

Biphasic action of sarin on monosynaptic reflex in the neonatal rat spinal cord in vitro.

The action of sarin, an organophosphorus (OP) compound, was examined in vitro for its effects on the spinal monosynaptic reflex (MSR) in neonatal rats. The effects of sarin were biphasic, i.e. facilitation at lower concentrations (2-20 nM) followed by depression of the MSR at concentrations above 30 nM. Facilitation of MSR was maximal (150% of control) at 20 nM sarin. The depression of MSR was maximal (70% of control) at 200 nM sarin, with half maximal inhibition occurring at 90 nM sarin. Atropine (200-500 nM) effectively reversed the depression caused by sarin, while pretreatment with low concentrations of atropine (10 nM) completely blocked the depression otherwise observed with sarin. Benactyzine was also effective in preventing sarin-induced depression, while pirenzepine was less effective. The nicotinic blocking agents tubocurarine and mecamylamine were, however, ineffective in preventing or reversing sarin-induced depression. The facilitation of MSR seen with lower concentrations (2-20 nM) correlated well with the blockade of late phase inhibition (between 30 and 50 ms conditioning-test interval) elicited in spinal cord by stimulating the adjacent dorsal root at various condition-test intervals, which has been shown elsewhere to be sensitive to bicuculline (Deshpande and Warnick 1988). Thus it is speculated that sarin at lower concentrations blocks GABA transmission, producing facilitation, and at higher concentrations activates the muscarinic receptors producing depression of MSR. The beneficial action of pretreatment with antimuscarinic agents may be attributed to the protection of the muscarinic receptors.

O-098 - Endogenous adenosine is involved in a depression of monosynaptic reflex during hypoxia in neonatal rat spinal cord

O-098 - Endogenous adenosine is involved in a depression of monosynaptic reflex during hypoxia in neonatal rat spinal cord

Cutaneous nerve-evoked cholinergic inhibition of monosynaptic reflex in the neonatal rat spinal cord: Involvement of M 2 receptors and tachykininergic primary afferents

The mechanisms of a cutaneous nerve-evoked inhibition of monosynaptic reflex were investigated in an isolated spinal cord-peripheral nerve preparation of the neonatal rat. Conditioning stimulation of the saphenous nerve, with five pulses at 50 Hz and a strength sufficient to activate C fibers, evoked an inhibition lasting about 20 s of the monosynaptic reflex that was elicited by stimulation of the nerve branch to quadriceps femoris muscle and recorded from the L3 ventral root. This inhibition of monosynaptic reflex was potentiated by an anticholinesterase, edrophonium, and mostly blocked by atropine. Application of acetylcholine, muscarine, bethanechol, carbachol, arecoline and oxotremorine induced an inhibition of monosynaptic reflex. From the effects of muscarinic antagonists, pirenzepine, AF-DX 116, and 4-diphenylacetoxy- N-methylpiperidine on the agonist-evoked and primary afferent-evoked inhibition of monosynaptic reflex it was concluded that the muscarinic receptors involved in the cutaneous nerve-evoked inhibition of monosynaptic reflex are of M 2 type. When monosynaptic reflexes were evoked by two successive stimuli with intervals of 15 ms to 1 s, the second response was smaller than the first. This depression of monosynaptic reflex became less pronounced when the reflex was reduced by application of oxotremorine or arecoline or by conditioning stimulation of primary afférents, suggesting that the inhibition of monosynaptic reflex is presynaptic in nature. The late phase of the cutaneous nerve-evoked inhibition of monosynaptic reflex (5–20 s after conditioning stimulation) was markedly depressed by a tachykinin antagonist, spantide. Perfusion of the spinal cord with capsaicin (1 μM) for 1 h also abolished the late phase of the inhibition. Application of capsaicin or substance P to the spinal cord induced an inhibition of monosynaptic reflex, and the inhibition was antagonized by spantide and atropine. Measurements of acetylcholine content in the perfusate of isolated rat spinal cords demonstrated that bath-applied substance P evoked a release of acetylcholine from spinal neurons. These results suggest that tachykininergic primary afferent C fibers excite cholinergic spinal neurons and the released acetylcholine inhibits the monosynaptic reflex by acting on the presynaptic muscarinic receptors on group Ia fibers.

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.

Hypnotic suggestion of analgesia induces a profound depression of monosynaptic reflexes in man

Hypnotic suggestion of analgesia induces a profound depression of monosynaptic reflexes in man

Effect of methamphetamine on rat spinal cord Dopamine receptor-mediated depression of monosynaptic reflex

The experiments were performed on spinal rats transected at C1. Intravenous administration of methamphetamine-HCl (MA-HCl, 2 mg/kg) and apomorphine-HCl (5 mg/kg) reduced the amplitude of the monosynaptic reflex (MSR), while the polysynaptic reflex was increased by methamphetamine. Depression of the monosynaptic reflex by both drugs was antagonized by haloperidol, but not by phentolamine. Depression of the monosynaptic reflex by methamphetamine was not antagonized by pretreatment with reserpine; however, the result was explained by the assumption that methamphetamine releases newly-synthesized dopamine or that methamphetamine may act directly on dopamine receptors. Depression of the monosynaptic reflex induced by methamphetamine was independent of peripheral changes in blood pressure. Oxygen tension in the spinal cord was slightly reduced by methamphetamine in rats treated with phentolamine and a change of pO 2 in the spinal cord was ruled out as a possible mechanism of action. These results suggest that dopaminergic neurons in the spinal cord of the rat depress the transmission of monosynaptic spinal reflexes.

Presynaptic inhibition of the monosynaptic reflex produced by injections of nicotine or eserine in the spinal cat

In completely deafferented cats with spinal cord transected and paralyzed with gallamine, the close arterial injection of nicotine (5 to 33 μg) into the spinal cord circulation or the intravenous injection of eserine (2 mg/kg) produced a transient increase in excitability of the central terminals of primary afferent fibers. Continuous d-c records from dorsal roots during nicotine injections indicated that a depolarization of the terminals was probably responsible for the observed excitability increase. Mecamylamine prevented both the depolarization and the increase in excitability of primary afferent central terminals whereas atropine and gallamine did not. The monosynaptic reflex was always depressed following injections of nicotine or eserine, but the excitability of the motorpool was found to be increased by these drugs. It was concluded that the monosynaptic reflex depression following injections of nicotine or eserine had a significant presynaptic inhibitory component as a consequence of a drug-induced depolarization of the central terminals of Group Ia afferent fibers.

Spinal cord effects of a brainstem cholinergic system

Eserine has been found to produce two patterns of lumbar monosynaptic reflex (MSR) alteration: the first pattern was MSR depression followed by return to control amplitude; the second pattern was a gradual depression of the reflex followed by partial recovery and then further depression followed by a gradual return to control amplitude. The lack of evidence of primary afferent depolarization and of sensitivity to picrotoxin indicated that the MSR depression was post-synaptic in nature. The eserine-induced alteration of the MSR was of brainstem origin. The alteration did not occur following spinal cord transection and was not sensitive to strychnine. A slight depression of the Renshaw cell firing rate indicated that the inhibition was not due to Renshaw cell activity. Medial longitudinal fasciculus lesions and cerebellectomy did not prevent or modify the eserine induced MSR alteration. Interneuronal destruction, accomplished by thoracic aorta ligation, did not prevent eserine-induced MSR depression. Spinal cord tracts mediating the eserine effect appear to travel in the lateral funiculus. Eserine produced spike activity in the nucleus reticularis pontis caudalis and a depression of neck muscle tone. Atropine sulphate reversed eserine-induced MSR alteration. It is thought that eserine (1) sensitizes a group of brainstem neurones, perhaps those in the Magoun inhibitory centre, to produce inhibitory postsynaptic potentials (IPSPs) on motoneurones, (2) triggers an episode of desynchronized sleep which produces a bombardment of IPSPs on motoneurones and (3) activates an independent system which results in MSR rebound or partial recovery from inhibition.

Red nucleus fast activity and signs of paradoxical sleep appearing during the extinction of experimental seizures

The electrical activity of several cortical and subcortical structures was analyzed in cats during electrically and pentamethylenetetrazol-induced seizures. These activities were compared with the spinal monosynaptic reflex variations during the same seizures. The following results are described: 1. 1. The monosynaptic spinal reflex is initially facilitated during the tonic phase and when it is elicited in the vicinity of a clonic wave. 2. 2. In the last stages of the seizure, the monosynaptic spinal reflex appears deeply inhibited. This inhibition coincides with the appearance of fast sinusoidal (15–40 c/sec) activity in the red nucleus. Often this activity exceeds the abrupt cortical end of the seizure. 3. 3. The electrical stimulation of red nucleus areas which show fast sinusoidal activity is also associated with a spinal monosynaptic reflex depression. 4. 4. The electrical stimulation of the cortical sensori-motor areas in which the tonic-clonic activity was recorded facilitates the monosynaptic spinal reflex. 5. 5. In the last stages of the convulsive activity, central and peripheral signs appear which are similar to those described for paradoxical or REM phase of normal sleep.