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J M Beaton

Publications and source records attributed to J M Beaton.

36 records · Page 2Linked to original sources
PubMed1975

The behavioral effects of L-methionine and related compounds in rats and mice.

Several groups of investigators have reported that the administration of L-methionine, with or without a monoamine oxidase inhibitor, induced an acute florid psychotic reaction in 40 percent of schizophrenics tested. The mode of action of L-methionine in brain is unknown, but may be via one or more of three mechanisms: the excess methionine (i) may lead to the production by transmethylation of some psychotomimetic methylated derivative of dopamine or serotonin, or (ii) could result in an increase in the levels of a metabolite of methionine (e.g., homocysteine, cystathionine, or cysteine), or (iii) may effect the cellular uptake of other amino acids. In order to test the first two hypotheses, L-methionine, betaine (another metyl group donor), L-methionine plus L-serine, L-cysteine, L-serine, and saline (as a control) were studied on the sleep-wake cycles of random-bred Swiss mice and on the avoidance behavior or rats. L-methionine plus L-histidine, L-methionine plus nicotinamide, L-histidine, and nicotinamide were also tested in the mice. Daily injections of 250 mg/kg of these compounds were administered for at least 21 consecutive days. Schedule performance in the rat and the sleep-wake cycles of the mice were monitored during this period and compared to controls. L-Methionine induced behavioral and sleep cycle disturbances which were removed by the simultaneous administration of L-serine but not by the addition of L-histidine or nicotinamide. These data suggest that the disruption may be due to an increase in the levels of one of the metabolities of methionine, homocysteine, rather than to an increase in the number of available methyl groups.

Animals↗
PubMedDate not supplied

The neurobehavioral effects of pralidoxime mesylate in the rat.

The neurobehavioral effects of pralidoxime mesylate (P2S) were characterized in the rat by comparing standard measures such as conditioned taste aversion, operant behavior and spontaneous locomotor activity. Male albino Sprague-Dawley rats were injected IP with either saline, 25, 50, or 100 mg/kg of P2S. None of these doses produced any overt toxic effects. P2S produced a conditioned taste aversion at the highest dose (100 mg/kg) using a single conditioning trial with sucrose in a one-bottle test. Acute administration of 100 mg/kg did not disrupt fixed ratio responding on a water reinforced schedule. All three doses, 25, 50, and 100 mg/kg, decreased spontaneous locomotor activity in a dose-dependent manner. The results of these studies support the findings that a single injection of P2S at the therapeutic levels would not disrupt the normal working performance in man.

Animals↗
PubMedDate not supplied

Behavioral toxicological assessment of oral pralidoxime methanesulfonate in the rat.

The behavioral toxicity of pralidoxime methanesulfonate (P2S) was examined in the rat by comparing standard measures such as conditioned taste aversion (CTA), drinking behavior and acute oral toxicity. P2S produced a weak CTA at doses of 0.4 and 0.8 g/kg (PO) and a profound CTA at the highest dose (1.6 g/kg) using a single sucrose-flavored conditioning trial with a one bottle test. The CTA produced by the highest dose of P2S was blocked by a specific, and exclusively peripheral, histamine-H2blocker, cimetidine (30 mg/kg, IP), which also has a cytoprotecting effect on gastric mucosal lesions. These data suggest that the H2 receptors may be involved in inducing the aversive effects of P2S through the inherent local irritating property of P2S on the rat gastric mucosa. There was no disruption of water drinking in thirsty rats with P2S at doses ranging from 0.2 to 1.6 g/kg. The survival time after an acute oral lethal dose of P2S (8-15 g/kg) was prolonged in non-fasted rats (16.5-38.5 min) compared to fasted ones (3.5-14.5 min), however the LD50's were identical (8.7 +/- 1.0 and 7.5 +/- 0.5 g/kg; respectively); indicating that P2S taken with food delays the lethal effects, but does not affect its lethal potency.

Administration, Oral↗