PubMed Health⌕ Search

Biomedical subjects

J G Sinclair

Publications and source records attributed to J G Sinclair.

At least 37 records · Page 2Linked to original sources
PubMed1980

Evidence against a serotonin involvement in the tonic descending inhibition of nociceptor-driven neurons in the cat spinal cord.

To determine whether serotonin (5-HT) is involved in the powerful tonic descending inhibition which exists on dorsal horn nociceptor-driven neurons, their response to a noxious stimulus was tested with drugs that enhance (fluoxetine) or decrease (p-chlorophenylalanine) 5-HT synaptic activity. Neither the response with the spinal cord intact nor the enhanced response with the spinal cord cold blocked was altered by these drugs. Thus we conclude that 5-HT is not involved in this tonic descending inhibition.

Animals↗
PubMed1980

The response of dorsal horn neurones of the cat to intraarterial bradykinin and noxious radiant heat.

In chloralose-anaesthetized or decerebrate cats intra-arterially administered bradykinin (BKN) and noxious radiant heat were tested on dorsal horn neurones characterized according to their responses to natural stimuli. Of the 28 neurones which were excited only to non-noxious forms of stimuli, BKN affected 4 while noxious radiant heat was ineffective. BKN also affected relatively few of the nociceptor-driven neurones (18 of 60) and most of these were inhibited, while noxious radiant heat excited the majority of these cells (47 of 60). Therefore, under our experimental conditions, noxious radiant heat would appear to be a more effective and specific noxious stimulus than BKN.

Animals↗
PubMed1980

The effect of naloxone on the inhibition of nociceptor driven neurones in the cat spinal cord.

The functional role of the opiate receptors and enkephalins found in high concentration in the superficial dorsal horn of the spinal cord has not been ascertained but may be the modulation of transmission in nociceptive pathways. In cats anaesthetized with alpha-chloralose the nacrotic antagonist, nalozone, was tested on various types of inhibitory input to spinal cord neurones which responded to both noxious and non-noxious stimulation of their receptive fields (Class 2 neurones). Naloxone (0.3-2.0 mg/kg i.v.) failed to alter the response of these neurones to noxious radiant heat, to tonic descending inhibition or to inhibition evoked by stimulation of the dorsal columns or contralateral plantar nerve. Thus the endorphins do not appear to be involved in mediating the types of inhibition examined. On the other hand, i.v. morphine reduced the response of Class 2 neurones to noxious heating of the skin that was reversed by naloxone.

Animals↗
PubMed1980

The effects of ethanol on cerebellar Purkinje cells in naive and alcohol-dependent rats.

In urethane-anesthetized rats, ethanol (1.5 g/kg, i.v.) increased the rate of discharge of cerebellar Purkinje cells, increased their regularity of discharge, and reduced or eliminated the climbing fibre evoked bursts. Most of the neurones responding in this manner exhibited an acute tolerance to the drug. Another group of rats was made alcohol dependent by feeding them for 2 weeks on a diet containing ethanol (12.5-16.5 g/kg per day). Ethanol produced similar but reduced effects on Purkinje cells of these animals.

Action Potentials↗
PubMed1978

Acute tolerance to ethanol on the release of acetylcholine from the cat cerebral cortex.

Ethanol (1 g/kg, iv) produced a peak depression of acetylcholine release from the cat sensorimotor cortices within 30 min of the ethanol administration but recovery to control levels occurred in the following 30 min. However, the concentrations of ethanol in the blood and in the solution bathing the cortex remained stable during this recovery period. This example of acute tolerance to ethanol is possibly related to the well-known acute tolerance that develops to the behavioural effects of ethanol.

Acetylcholine↗
PubMed1977

Tonic inhibitory influence of a supraspinal monoaminergic system on presynaptic inhibition of an extensor monosynaptic reflex.

Presynaptic inhibition of the extensor (quadriceps, QUAD) monosynaptic reflex (MSR) in unanaesthetized decerebrate cats was antagonized by imipramine hydrochloride (2-5 mg/kg), 5-hydroxytryptophan (75 mg/kg) and a specific 5-hydroxytryptamine (5-HT) neuronal uptake blocker, fluoxetine hydrochloride (Lilly 110140, 0.25-6 mg/kg). These effects of imipramine and fluoxetine were partially reversed by the 5-HT antagonist, cyproheptadine hydrochloride (5 mg/kg), and completely reversed by the application of a thoracic cold block which prevents supraspinal inputs to the caudal spinal cord. Imipramine, however, failed to antagonize this inhibition in animals pretreated with either DL-p-chlorophenylalanine (p-CPA, 300 mg/kg i.p. for 2 consecutive days) or DL-a-methyl-p-tyrosine methyl ester hydrochloride (a-MPt, 125 mg/kg i.p. 16 and 4 h prior to the experiment). Cyproheptadine (2.5--5 mg/kg); phenoxybenzamine hydrochloride (2.5-5 mg/kg) and a cold block enhanced the inhibition of this extensor MSR but a cold block failed to alter the inhibition in animals pretreated with p-CPA or a-MPT. Presynaptic inhibition of the flexor (posterior biceps-semitendinosus, PBST) MSR was however not blocked by imipramine, fluoxetine or a cold block nor enhanced by cyproheptadine or phenoxybenzamine. The effects of the drugs tested and a cold block on the excitability of the QUAD group Ia afferents were reciprocal to those on the MSR during presynaptic inhibition. The results of this study indicate that descending tonically active systems (1) involving 5-HT and noradrenaline, antagonize presynaptic inhibition of the QUAD but not the PBST-MSR, (2) decrease the excitability of the QUAD Ia afferents and (3) increase the excitability of QUAD motoneurones.

5-Hydroxytryptophan↗
PubMed1977

The blockade of serotonin uptake into synaptosomes:relationship to an interaction with monoamine oxidase inhibitors.

To test the hypothesis that the hyperpyrexia produced by meperidine and detromethorphan in rabbits pretreated with a monoamine oxidase inhibitor is related to inhibition of neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)), fluoxetine (Lilly 110140) was studied. This potent and specific 5-HT neuronal uptake blocker was administered to phenelzine-pretreated rabbits and found to produce a lethal hyperpyrexia in doses equal to or greater than 2.5 mg/kg. The order of potency in blocking 5-[14C]HT uptake into synaptosomes prepared from rabbits was: fluoxetine greater than meperidine = dextromethorphan = levorphanol greater than anileridine greater than alphaprodine greater than morphine. Since fluoxetine, meperidine, and dextromethorphan produce hyperpyrexia in phenelzine-pretreated rabbits, whereas anileridine, alphaprodine, and morphine do not, there appears to be some correlation between the hyperpyrexic response and inhibition of 5-HT uptake. The exception is levorphanol, which is not hyperpyrexic despite being equipotent with meperidine and dextromethorphan in inhibiting 5-HT uptake. The ineffectiveness of levorphanol in producing hyperpyrexia may be due to its marked depressant properties, since the addition of another depressant drug (pentobarbital) antagonized the hyperpyrexic effect of meperidine.

Analgesics, Opioid↗
PubMed1976

Tonic inhibitory influence of a supraspinal monoaminergic system on recurrent inhibition of an extensor monosynaptic reflex.

Recurrent inhibition of the extensor (quadriceps) monosynaptic reflex (MSR) was antagonized by a 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP, 75 mg/kg), and a specific 5-HT neuronal uptake blocker, fluoxetine-HC1 (Lilly 110140, 0.25-6 mg/kg), in unanaesthetized decerebrate cats. This inhibition of the flexor (posterior biceps-semitendinosus) MSR was not altered by fluoxetine. Cyproheptadine-HC1 (5 mg/kg) partially reversed the above blocking actions of 5-HTP and fluoxetine and a thoracic "cold block", which eliminates supraspinal inputs to the caudal spinal cord, also eliminated the blockade by fluoxetine on recurrent inhibition. Cyproheptadine (2.5-5 mg/kg) or phenoxybenzamine-HC1 (2.5-5 mg/kg), administered alone, enhanced recurrent inhibition of the extensor but not of the flexor MSR. Since a "cold block" increased recurrent inhibition of the extensor reflex in control animals but failed to alter the inhibition in animals pretreated with either DL-p-chlorophenylalanine (300 mg/kg i.p. for 2 consecutive days) or DL-a-methyl-p-tyrosine methyl ester-HC1 (125 mg/kg i.p. 16 and 4 h prior to experiment), the monoaminergic system would appear to be tonically active. In addition the neuronal uptake blocker, imipramine-HC1 (0.125-4 mg/kg), was more potent in antagonizing recurrent inhibition when injected intra-arterially to the spinal cord than when administered intra-arterially to the brain stem or intravenously, indicating that this agent acts in the spinal cord to block the inhibition. These results support our previous proposal (ref. 18) that a supraspinal system involving 5-HT and noradrenaline antagonizes recurrent inhibition of the quadriceps MSR. This monoaminergic system is tonically active with the 5-HT nerve terminals located in the spinal cord.

5-Hydroxytryptophan↗
PubMed1976

Serotonin involvement in the blockade of bulbospinal inhibition of the spinal monosynaptic reflex.

Bulbospinal inhibition of the extensor quadriceps monosynaptic reflex (MSR) was antagonized by the serotonin precursor, 5-hydroxytryptophan (5-HTP, 75 mg/kg), in unanesthetized, mid-collicular, decerebrate cats. Fluoxetine HCl (Lilly 110140, 0.25 - 6 mg/kg), a specific serotonin neuronal uptake blocker, also blocked this inhibition as well as bulbospinal inhibition of the flexor posterior biceps-semi-tendinosus MSR. The serotonin antagonist, cyproheptadine HCl (5 mg/kg), partially reversed the above blocking actions of 5-HTP and fluoxetine and enhanced bulbospinal inhibition when administered alone in doses of 2.5-5 mg/kg. Imipramine HCl (0.125 - 4 mg/kg) was more potent in antagonizing bulbospinal inhibition of the dorsal root-ventral root MSR when administered intra-arterially to the spinal cord than when injected intra-arterially to the brain stem or intravenously, indicating that the spinal cord is the site of imipramine's action. These results support our earlier proposal that a 5-HT system antagonizes bulbospinal inhibition of the MSR. They also indicate that the 5-HT system is tonically active and exerts its blocking action in the spinal cord.

5-Hydroxytryptophan↗