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M J Rowan

Publications and source records attributed to M J Rowan.

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Changes in auditory evoked responses and in the inhibitory action of 5-hydroxytryptophan following chronic treatment with imipramine in the rat.

The neurophysiological effects of acute and chronic treatment with the tricyclic antidepressant drug imipramine were investigated. Brainstem (BAER) and middle latency (MLR) auditory evoked responses were monitored in the alert and immobile rat. Daily injection of imipramine (10 mg/kg, IP) for 2 weeks produced a 13% increase in the latency and a 35% reduction in the amplitude of the N17 component of the MLR. Acute imipramine treatment had no effect. There was no observable change in the BAER after either acute or chronic drug administration. Serotonergic function was assessed by studying the inhibitory effects of 5-hydroxytryptophan on the BAER and MLR. Chronic application of imipramine caused an apparent reduction of the effects of 5-hydroxytryptophan (75 mg/kg, IP) on the N17 component of the MLR. This may, however, be due to the shift in baseline latency and amplitude. Inhibition of the BAER by 5-hydroxytryptophan was unaltered by long term exposure to imipramine. Acute treatment with imipramine was without effect on the modulation of the BAER and the MLR by 5-hydroxytryptophan. These results provide evidence that chronic, as opposed to acute, administration of imipramine had an inhibitory effect on auditory processing at the level of the MLR and that this may be associated with a change in the net output of the serotonergic system.

5-Hydroxytryptophan↗

Enhancement of long-term potentiation by the calcium channel agonist Bayer K8644 in CA1 of the rat hippocampus in vitro.

The effect of the Ca agonist BAY K8644 was studied on long-term potentiation (LTP) of extracellular excitatory postsynaptic potentials in the stratum radiatum of CA1 of the hippocampus in vitro. LTP was evoked by brief trains of high-frequency stimulation applied to the stratum radiatum of CA1. 0.5% Ethanol, the vehicle used to dissolve BAY K8644, reduced LTP from 43% to 15%. An amount of 15 microM BAY K8644, in 0.5% ethanol, enhanced LTP from 13% in the ethanol control to 57%. The Ca channel antagonist verapamil did not alter control LTP, but did inhibit the potentiating action of BAY K8644 on LTP. It is postulated that the enhancement of LTP by BAY K8644 may occur through enhancement of Ca influx through voltage-dependent Ca channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Neurophysiological effects of buspirone and isapirone in the hippocampus: comparison with 5-hydroxytryptamine.

The neurophysiological effects of two novel anxiolytic compounds, buspirone and isapirone (TVX Q 7821), were compared with those of 5-hydroxytryptamine (5-HT) on the population spike in the CA1 region of the rat hippocampal slice. Micromolar concentrations of the two drugs mimicked the inhibitory effect of 5-HT but unlike 5-HT they did not produce any significant excitation. In slices in which 5-HT was purely excitatory, there was a marked reduction in the inhibitory response to these agents. The effect of isapirone was antagonised by spiperone. These results suggest that buspirone and isapirone are agonists for 5-HT1A receptors in the hippocampus.

Animals↗

Effects of methylglyoxal on central and peripheral cholinergic responses.

Methylglyoxal (MG) has been shown to have a depolarizing effect on the giant interneurones of the isolated 6th abdominal ganglion of the cock-roach. This effect of MG was inhibited by concentrations of nicotine, d-tubocurarine and physostigmine which blocked transmission at the cholinergic cercal nerve-giant interneurone synapse. MG (5 X 10(-5) to 5 X 10(-4) M) produced concentration-dependent contractures of the isolated frog rectus abdominis muscle which were inhibited by d-tubocurarine (10(-4) M) and physostigmine (10(-6) M). MG enhanced the action of acetylcholine and inhibited KCl-evoked contractures whereas it had no effect on the response to carbachol. It is concluded that MG appears to act as a cholinomimetic in both the peripheral and central nervous systems.

Aldehydes↗

The effects of methylglyoxal on central synaptic transmission in the isolated nerve cord of the cockroach. (Periplaneta americana L).

Methylglyoxal (10(-5) to 1.5 X 10(-4) M) was found to have excitatory effects on synaptic transmission in the isolated 6th abdominal ganglion of the cockroach. There was a concentration-dependent depolarization of the giant interneurones which was accompanied by an increase in the amplitude and duration of electrically evoked excitatory postsynaptic potentials. The frequency of spontaneous activity was also increased.

Aldehydes↗

The effect of prolonged treatment with tricyclic antidepressants on the actions of 5-hydroxytryptamine in the hippocampal slice of the rat.

The effect of long-term treatment with the tricyclic antidepressants imipramine (IMI) and desmethylimipramine (DMI) on neuronal responsiveness to 5-hydroxytryptamine (5-HT) was examined in the hippocampal slice preparation from the rat. Population spikes, evoked by electrical stimulation of the stratum radiatum, were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. When 5-HT (10(-7) to 2 X 10(-5) M) was applied there was an initial increase followed by a decrease in the amplitude of the population spike. On washout of 5-HT the amplitude increased transiently above control levels. Daily injection of 10 mg/kg of imipramine or desmethylimipramine, intraperitoneally, into rats for 4-5 weeks was found to produce a significant decrease in the inhibitory effect of 10(-5) M 5-HT, whereas there was no apparent change in the excitatory effects. The acute application of 10(-5) M imipramine or desmethylimipramine antagonized the inhibitory effect of 10(-5) M 5-HT without affecting the excitatory effects. Acute application of the 5-HT receptor antagonists cyproheptadine (10(-5) M) and ketanserin (7.5 X 10(-6) M) completely prevented the appearance of the inhibitory effect of 10(-5) M 5-HT without affecting the excitatory effects. It was concluded that the decreased inhibitory effect of 5-HT which was produced by chronic treatment with imipramine or desmethylimipramine was probably due to a reduction in the number of 5-HT receptors or a reduction in the post-receptor effector mechanisms for 5-HT.

Animals↗

Frequency-dependent block of field potentials in the rat hippocampal slice caused by tricyclic antidepressants.

The effect of the tricyclic antidepressants imipramine and desipramine were studied on field potentials in the rat hippocampal slice. The electrically evoked stratum radiatum nerve volley, excitatory postsynaptic potential (e.p.s.p.) and pyramidal cell layer population spike (PS) were recorded in the CA1 region. At concentrations of 10(-6)M to 10(-5)M, impramine did not affect the amplitude of the nerve volley, e.p.s.p. or PS at low frequencies of stimulation (0.01 Hz). At higher frequencies of stimulation (1-100 Hz), imipramine caused a frequency-dependent block of the nerve volley, e.p.s.p. and PS. The time course of onset of the frequency-dependent block in the presence of imipramine was very slow. Maximum inhibition was reached after 3-4 h treatment with imipramine. Desipramine (10(-6)-10(-5)M) also caused a frequency-dependent block of the hippocampal field potentials. Only slight frequency-dependent block was observed in slices from rats injected in vivo with desipramine (10 mg kg-1) for 14 days.

Action Potentials↗

Neurophysiological evidence for tricyclic antidepressant-induced decreased beta-adrenergic responsiveness in the rat hippocampus.

A study was made in rats of the effects of chronic treatment with the tricyclic antidepressant agent imipramine on the increase in the population spike amplitude produced by the beta-adrenergic receptor agonist isoproterenol in the 'in vitro' slice preparation of the hippocampus. A significant reduction of 39% and 44% of the population spike increase was observed at 5 X 10(-7) M and 1 X 10(-6) M isoproterenol respectively in rats treated for 28 days with 10 mg/kg i.p. imipramine.

Action Potentials↗

The toxicity of p-benzoquinone on the central nervous system of the cockroach.

The behavioural symptoms of acute-p-benzoquinone intoxication in the cockroach were shown to be an initial excitation followed by rigid paralysis. p-Benzoquinone produced a depolarization of the postsynaptic membrane of the giant neurones in the 6th abdominal ganglion of the cockroach which was accompanied by an increase in the electrically evoked excitatory postsynaptic potential. The frequency and amplitude of unitary postsynaptic potentials also increased. These effects may be due to inhibition of active cation transport, as illustrated here on the frog isolated skin.

Animals↗

Ultrastructural changes induced by p-benzoquinone in the terminal abdominal ganglion of the cockroach.

The morphology of the sixty abdominal ganglion, associated connectives and cercal nerves was examined using an electron microscope after acute treatment of the isolated tissue with 0.5 mM p-benzoquinone. A high incidence of mitochondrial damage was observed in all three regions of the tissue. This may be due to a metabolic inhibitory action or a pro-oxidant action of p-benzoquinone.

Abdomen↗

7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Nitric oxide (NO) is an intercellular messenger that has been suggested to have a role in learning and memory formation. Previous studies with nonselective NO synthase inhibitors have produced contradictory results in learning experiments. However, these drugs also produced blood pressure changes, as NO is an endothelial-derived relaxing factor. A novel NO synthase inhibitor, 7-nitro indazole (7-NI), as a dose (30 mg/kg i.p.) shown previously to inhibit neuronal NO synthase by 85% without affecting blood pressure, produced amnesic effects both in a water maze and in an 8-arm radial maze. Latency as well as distance was greater in the 7-NI group in the water maze while swim speed was not affected. Latency, working memory (WM), and reference memory (RF) errors were also higher in the 7-NI group in the 8-arm maze. At the end of the second training day, these differences were no longer apparent. However, on the fourth training day, a transfer test in the water maze showed that 7-NI had produced a spatial memory deficit, reducing quadrant bias and the number of annulus crossings. Learning of a visual cue task was not affected. No difference between groups was visible in an open field test. We conclude that neuronal NO synthase activity plays a role in learning and memory formation in the rat.

Animals↗

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

We report here that release of glutamate, inositol phospholipid metabolism, and protein kinase C (PKC) activity are increased in synaptosomes prepared from hippocampi of rats that had been trained in a spatial learning task. In hippocampi obtained from animals that were untrained, activation of the metabotropic glutamate receptor by the specific agonist trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD) increased release of glutamate but only in the presence of a low concentration of arachidonic acid. A similar interaction between arachidonic acid and ACPD was observed on inositol phospholipid turnover and on PKC activity. However, the synergistic effect of arachidonic acid and ACPD on glutamate release was occluded in hippocampal synaptosomes prepared from trained rats. Occlusion of the effect on inositol phospholipid turnover and PKC activation was also observed. These data suggest that the molecular changes that underlie spatial learning may include activation of metabotropic glutamate receptors in the presence of arachidonic acid and that the interaction between arachidonic acid and ACPD triggers the presynaptic changes that accompany learning.

Animals↗

The assessment of neurotoxicity using the cockroach nerve cord.

The acute central nervous system toxicity of chemicals may be detected and analysed with relative ease in the isolated abdominal ventral nerve cord of the American cockroach. Stable electrophysiological measurements of axonal and both inhibitory and excitatory synaptic transmission can be made for several hours with extracellular electrodes using a mannitol-gap technique. Dose-response curves can be obtained for the effects of the chemicals. These can be analysed in terms of site of action, be it on the axons, the presynaptic nerve terminal, the postsynaptic receptors or the termination of neurotransmitter action. Possible non-specific sites are also considered.

Animals↗