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Biomedical subjects

J G Sinclair

Publications and source records attributed to J G Sinclair.

At least 19 recordsLinked to original sources
PubMed1992

Responses in the CA1 region of the rat hippocampus to a noxious stimulus.

We report here some physiological and pharmacological characteristics of noxious stimuli-induced changes in the hippocampal CA1 pyramidal cell synaptic excitability to field CA3 stimulation. A noxious heat stimulus applied to the left hind paw (LHP) produced a persistent depression of the CA1 population spike (PS) which habituated to a repetition of the stimulus. Interestingly, exposure of the tail to a noxious stimulus following habituation of the LHP produced a depression of the CA1 PS. This finding suggested that persistent depression and habituation are topographically represented. In separate experiments we determined that while the persistent depression of the CA1 population spike was accompanied by, in most cases, a prolonged increase in the amplitude of the CA1 antidromic field potential, there was a concurrent persistent depression and habituation of the CA1 PS and the corresponding apical dendritic field excitatory postsynaptic potential (dfEPSP). This suggested that noxious stimulus-induced CA1 synaptic depression is mediated at the apical dendritic region, perhaps postsynaptically at the dendrites and/or presynaptically on CA3 afferent terminals. Furthermore, atropine sulfate (40 mg/kg ip), which prevented the depression of the CA1 PS, also blocked the depression of dfEPSP when iontophoresed at the apical dendritic recording site. In addition atropine antagonized the depression of the dfEPSP produced by iontophoretic acetylcholine (Ach) but not gamma-aminobutyric acid. However, iontophoretic atropine at the cell body recording site did not prevent the depression of the CA1 PS. These results are consistent with the notion that Ach release in the apical dendrites of CA1 pyramidal cells following a noxious stimulus depresses CA1 synaptic excitability.

Analysis of Variance↗
PubMed1988

A simple microcomputer interface for tail-flick determination.

An inexpensive means of tail-flick latency data acquisition and analysis using an Apple IIe microcomputer and three simple interface circuits is described. Descriptions of the software and hardware are provided with schematics and program listings. The measurement, storage, and analysis of the data are integrated in one system.

Animals↗
PubMed1988

Fluoxetine and pargyline on the nucleus raphe magnus inhibition of cat multireceptive dorsal horn neurones.

1. To determine whether serotonin (5-HT) is involved in the nucleus raphe magnus (NRM) inhibition of cat multireceptive dorsal horn neurones, the NRM inhibition was tested with drugs (fluoxetine and pargyline) that should enhance 5-HT synaptic activity. 2. Fluoxetine and pargyline systemically administered, individually or concurrently, decreased rather than increased the inhibition. 3. The results do not support the hypothesis that NRM stimulation-produced inhibition is mediated by 5-HT release.

Animals↗
PubMed1987

The failure of morphine to interact with serotonin on nucleus raphe magnus descending inhibition or morphine-induced suppression of cat spinal cord multireceptive neurones.

Morphine sulphate, administered in three cumulative doses (0.5, 1.0, and 2.0 mg/kg, i.v.) to alpha-chloralose anaesthetized cats, reduced the nociceptive activity of deep dorsal horn multireceptive neurones but failed to alter the descending nucleus raphe magnus (NRM) phasic inhibition of these neurones. Morphine was also administered to fluoxetine (6.0 mg/kg, i.v.) pretreated animals. Fluoxetine is a selective 5-hydroxytryptamine (5-HT) uptake blocker, which should enhance 5-HT synaptic transmission. In these animals, morphine suppressed the neuronal nociceptive activity to the same extent as seen with morphine alone and did not affect the NRM inhibition. These results do not support the notion that morphine activates a descending serotonergic inhibition from the NRM or that serotonin mediates morphine inhibition of spinal nociceptive transmission in cats.

Animals↗
PubMed1986

Morphine, but not atropine, blocks nociceptor-driven activity in rat dorsal hippocampal neurones.

Neurones in the CA1 region of the dorsal hippocampus of urethane-anaesthetized rats were recorded extracellularly with microelectrodes, and tested for their response to non-noxious and noxious peripheral stimuli. None of the cells responded to non-noxious stimuli but 91 of 216 cells were excited by noxious stimuli. Morphine (5.0 mg/kg i.v.) increased the background firing rate in 7 of 10 cells tested and blocked the response to noxious heating of the tail in all cases. Naloxone (0.5 mg/kg i.v.) reversed these effects of morphine. Atropine (0.1 plus 0.2 mg/kg i.v.), in another group of animals, produced only transient changes of an inconsistent nature in 7 cells tested.

Animals↗
PubMed1986

The failure of morphine to attenuate spinal cord nociceptive transmission through supraspinal actions in the cat.

Morphine sulphate was perfused between the third ventricle and cisterna magna in alpha-chloralose anaesthetized cats while recording from multireceptive dorsal horn neurones activated by peripheral noxious radiant heat. Morphine concentrations of 10(-5) and 10(-4) M were without effect, while 10(-3) M resulted in an increase in the spinal cord neuronal responses. The results do not support the notion that morphine activates a supraspinal mediated descending inhibition which antagonizes spinal cord nociceptive transmission.

Animals↗
PubMed1986

Ethanol blocks tetanic and calcium-induced long-term potentiation in the hippocampal slice.

Long-term potentiation (LTP) of the CA1 population spike in the hippocampal slice was produced by a tetanic stimulus in the stratum radiatum or by doubling the calcium concentration in the medium to 4 mM for 10 min. Ethanol (0.1 M) antagonized both tetanic- and ethanol-induced LTP. Since the hippocampus is known to be involved with memory, and ethanol interferes with memory and the production of LTP, the results are consistent with the notion that LTP may be related to memory processes.

Animals↗
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↗