International journal of neuropharmacology最新文献

The amino acids tryptophan and methionine are known to be involved in behavioral alterations and their metabolites have been implicated in mental illness. To learn more about the metabolic interrelationships of these two amino acids, rats were placed on amino acid diets deficient in nicotinic acid and nicotinamide and pair-fed with and without intestinal-antibiotics. Excess methionine (4%) added to such diets resulted in rats showing a decrease in body weight and urinary N¹-methylnicotinamide (MNA) and an increase in urinary xanthurenic acid (XA) and total indoleacetic acid (TIAA) in comparison with controls. Urinary creatinine (CR) was relatively unchanged. Intestinal-antibiotics did not affect the overall methionine effect. The overall results demonstrate that excess-dietary methionine alters the tissue metabolism of tryptophan, and gives rise to urinary excretion patterns of tryptophan metabolites claimed to occur in mental illness. The observed data point to a metabolic alteration involving vitamin B₆. A natural competition may exist between methionine and tryptophan for vitamin B₆ which is utilized in the metabolic pathways of both amino acids. Our work suggests that tolerance load tests of methionine and tryptophan in behavioral alteration studies must take into account the metabolic competition between these two amino acids for vitamin B₆, as well as the formation of psychotogenic metabolites by N-methylation and O-methylation reactions.

The effect of reserpine and p-chlorophenylalanine (PCPA) on the integrated voltage of the electrocorticogram (ECoG) of unrestrained rats was examined during 15 min and 2½ hr recording sessions. As previously reported, reserpine caused an increase in the ECoG voltage during 15 min sessions. This effect was slightly enhanced by PCPA pretreatment. PCPA treatment alone produced an increase in the ECoG voltage and an increase in synchronized activity similar to that induced by reserpine. Thus, it appears that the ECoG effect of reserpine during 15 min recording sessions does not depend upon increased “free” 5-HT. During 2½ hr sessions, PCPA produced a decrease in voltage with decreased slow-wave activity. A consistent increase in ECoG voltage was observed 4 hr after reserpine injection using the long recording time. By 24 hr, the voltage had returned to the control levels and was lower than the control at 48 hr and later. α-Methyltyrosine restored the decreased voltage to the control levels. PCPA pretreatment antagonized the reserpine-induced increase in ECoG voltage and instead of a return to the control at 24 hr after reserpine, a marked decrease in voltage was seen in the PCPA-pretreated animals at this time period. These results are discussed in terms of reciprocally acting “catecholaminergic” and “serotoninergic” systems.

The spontaneous and hypothalamically evoked discharge patterns of the preganglionic cervical sympathetic, splanchnic and vagal nerves have been described and discussed as potential indicators of central “autonomic tone” in cat. Chlorpromazine and diazepam, in i.v. doses of 0·3-3 mg/kg, generally reduced slightly spontaneous evoked impulse traffic in cervical sympathetic fibers, but markedly attenuated the electrical activity in splanchnic nerves. Vagal efferent activity was more subtly affected by these two agents. Pentobarbital (3–10 mg/kg i.v.) depressed spontaneous and evoked potentials in the sympathetic and vagal nerves. In addition, it prevented the poststimulatory inhibition observed in sympathetic nerves.

Rats receiving haloperidol for three days showed a dose dependent decrease of brain catecholamines. The hypothermic effect of the drug did not cause this. Haloperidol counter-acts the monoamine depletion of reserpine in both the brain and the heart provided it is given shortly before reserpine.

Although considerable attention has been directed towards the effects of cerebral cortical damage on convulsive thresholds, few studies have involved subcortical structures. In the present report, the thresholds for flurothyl-induced myoclonic jerks and generalized seizures were determined in adult, male albino rats. Bilateral lesions of the lateral geniculate nucleus resulted in an almost 20% decrease in threshold to the convulsant. Although no sensitivity changes resulted from lesions of either the lateral thalamic posterior nucleus or the medial geniculate nucleus, lesions of these areas potentiated the effects seen with lesions of the lateral geniculate nucleus alone. In all cases, the increased sensitivity to the convulsant required more than 1 week after surgery for development. It was concluded that the visual system is intimately involved in at least some types of convulsive phenomena.

Rats which had been chronically treated with sodium barbitone showed an increased running time for a food reward in a multiple “T” maze compared with untreated animals. The daily food intake and body weight were also significantly greater in the barbiturate treated animals. ACTH partially antagonized these effects of barbitone although it did not significantly affect the maze running time of rats which had not been treated with the barbiturate. It is suggested that ACTH antagonizes sodium barbitone by acting on the central nervous system and not as a consequence of its action on the pituitary-adrenal axis. Amphetamine did not antagonize the effect of barbitone on maze behaviour.

The inhibition of nociceptive reactions by cholinomimetic agents was studied in mice, rats and rabbits using systemic, intraventricular and intracerebral drug application. Tertiary amines (oxotremorine, arecoline and RS 86) as well as a quaternary ammonium compound (carbachol) were used. Various nociceptive reactions showed considerable differences in sensitivity. However, no clear-cut relation to the proposed level of integration of these reactions in the CNS could be found. Carbachol, which hardly passes the blood-brain barrier, was found after systemic administration to be ineffective against nociception but highly effective when injected intraventricularly in rats and rabbits. Oxotremorine too revealed a high antinociceptive activity when injected in this way. This points to a periventricular site of the antinociceptive action of cholinomimetics. Intracerebral microinjection of cholinomimetics into various brain structures of rats was very effective when injection was made into certain diencephalic and mesencephalic areas, but was much less effective when applied to the caudate nucleus. Similarities and differences between the antinociceptive action of cholinomimetics and morphine-like analgesics are discussed in view of the hypothesis that both groups of substances interfere with different links of periventricular nociceptive systems.

The effect of orphenadrine hydrochloride on the concentration of acetylcholine in the rat brain was investigated. An i.p. dose of 50mgkg caused a significant reduction of the acetylcholine concentration, as shown by determinations at 15 min—where the effect was maximal—and at 30 and 60 min after administration. These findings are discussed in relation to the orphenadrine concentration in the rat brain as a function of time and to other effects of the compound on brain biochemistry as previously established.

The rapid uptake of³HNE exhibitedin vitro by rabbit irises depends on the presence of sympathetic nerves and the NE concentration in the incubation medium. Pretreatment of the animals with reserpine and pargyline fails to inhibit the efficiency of this neuronal uptake process, thus confirming previous reports in the literature that the depletion of neuronal NE elicited by reserpine is not the result of the blockade of the uptake of NE by sympathetic neurons.