Progress in neuro-psychopharmacology最新文献

1. Brain uptake of tryptophan is regulated in part by competition from other plasma amino acids, e.g. leucine.

2. Following oral L-leucine loading, plasma leucine clearance was normal in 3 depressives but decreased in one depressive who subsequently reacted to L-tryptophan treatment.

3. It is suggested that a disturbed leucine clearance causes dietary leucine to remain elevated in plasma and that this effect, in turn, reduces brain uptake of tryptophan, and serotonin synthesis.

1. Melatonin was coupled to albumin by means of a N_a-p-carboxybenzyl, a N_a-propionic acid, methylene, or a diazotized p-aminobenzoic acid bridge and injected into rabbits or sheep.

2. All coupling procedures stimulated antisera which bound melatonin with the greatest affinity; N-acetylserotonin and 6-hydroxymelatonin cross-reacted with the antisera at 3–5%. Other naturally occurring indolealkylamine derivatives showed less cross-reactivity.

3. Coupling the hapten melatonin to protein through a bridge at or near the indole N can stimulate antisera which are relatively specific to melatonin and suggest that antisera which bind specifically to any other individual indolealkylamine derivative could be produced using these coupling procedures.

4. Using the methylene bridged antisera, a radioimmunoassay for melatonin was developed and validated for rat serum. In addition to tests for reliability and parallelism, serum estimates of melatonin by radioimmunoassay correlated .98 with gas chromatography-mass spectrometry.

5. Serum melatonin levels have a characteristic 24-hour rhythm with a crest late in the dark period (L:D 12:12). Following the injection of 50 ug of melatonin, serum levels reach 5–20 fold higher concentrations than physiological levels.

1. The regional formation rates of conjugated DHPG and MHPG in rat brain were estimated by determining their rates of accumulation following probenecid administration.

2. Brain regional conjugated DHPG formation rates correlated significantly with the regional steady state levels. This did not apply in the case of conjugated MHPG.

3. The formation rates of conjugated DHPG significantly exceeded those of conjugated MHPG in hypothalamus, midbrain, brainstem, hippocampus and cerebral cortex.

4. These findings clearly indicate that conjugated DHPG formation is the major route of rat brain NE metabolism and also suggests DHPG levels are more indicative of rat brain NE turnover, under resting conditions.

1. A liquid chromatography-electrochemical detection (LC-EC) assay for brain normetanephrine (NMN) has been developed which also allows concurrent determination of brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) concentrations.

2. Tissue samples were prepurified by cation exchange chromatography and the amines then separated by reversed-phase liquid chromatography on an octylsilane stationary phase.

3. This method permits measurement of at least 200 pg of the above amines in brain.

4. The concentrations of NMN in rat and mouse brain regions were found to be in the range of 0.115–0.435 ng/mg protein.

1. After an acute mild swim (20°, 3 min), levels of β-endorphin-like immunoreactivity decreased in the anterior pituitary to 48% of controls and in the intermediate-posterior pituitary to 62%. In the brain, of the 14 regions examined, four showed remarkable increases: central n. of amygdala to 167%, n. interstitialis striae terminalis to 174%, n. raphe dorsalis to 170%, and n. paraventricularis to 136%.

2. An acute severe swim (4°, 3 min) caused a decrease of the opioid to 66% and 93% of controls in the anterior and intermediate-posterior pituitary, respectively, and an increase in central n. of amygdala to 227%, in n. interstitialis striae terminalis to 173%, in n. raphe magnus to 148%, in n. paraventricularis to 155%, and in periaqueductal gray (PAG) to 193%.

3. Mild swimmings applied chronically for 21 days resulted in return of the opioid levels nearly to control values as habituation developed.

4. After chronic swimmings of gradually increased severity during the 21 day period (water temperature gradually decreased from 20° to 4° and the time of swimming gradually increased from 3 to 9 min), no habituation occurred but further increases in β-endorphin-like immunoreactivity were observed.

5. The present results show that stress of swimming affects pituitary and brain levels of β-endorphin and that in brain, the most affected are areas of midbrain and limbic structures. These effects are reversed by repeated exposure to mild swimming conditions, but not when the conditions of swimming gradually increase in severity.

1. Nine schizophrenic patients with florid symptoms were treated openly with d-propranolol. The mean dose was 1329 mg/day and the mean duration of treatment was 3.1 weeks.

2. Results showed seven out of nine patients improved. Significant change in the schizophrenia subscore of BPRS was observed. Side effects of concern were seen in two patients.

3. The implications of this therapeutic effect are discussed.

1. Haloperidol plasma levels, after long acting haloperidol i.m. injection, are analyzed and compared with clinical evolution and EEG modifications.

2. Haloperidol plasma levels were determined by radioimmunoassay. Clinical status was assessed weekly and computerized EEG were performed daily from day 3 to 7 after haloperidol decanoate injection.

3. The plasma level-dose relationship during oral treatment and 4 weeks after haloperidol decanoate injection are very similar. After injection, the plasma level attains its highest value within 3 to 10 days and decreases along a logarithmic curve. An inverse relationship with B.P.R.S.scores is found in many patients. EEG changes are related to clinical status rather than to plasma levels.

4. The results obtained by these three methods are proposed as criteria for the assessment of the reinjection time.

1. This pilot study examined physiological concomitants of lactate-precipitated panic in six patients selected according to DSM-III criteria for panic disorder.

2. Electrophysiological measures of central, autonomic and skeletal-muscular activities were monitored during a baseline period, i.v. administration of 5% D/W and of 0.5 M sodium lactate.

3. Panic episodes were elicited in all patients following lactate administration. Marked increases in HR, EOG and EMG together with EEG alpha reduction, P₂-N₂ amplitude reductions of the AEP and paradoxical increases in EEG delta activity indicate that experimentally induced panic states are characterised by physiological hyperarousal.

1. Levels of noradrenaline, dopamine and dopamine metabolites were measured in the striatum, limbic system and hypothalamus of amygdala-kindled and yoked control rats.

2. Subjects were sacrificed three weeks after the kindled animals had displayed their fifth “Stage 5” generalized convulsion.

3. No significant differences between kindled and control brains were found in any region except the hypothalamus. In the hypothalamus, noradrenaline and dopamine levels were significantly elevated in the kindled tissue. DOPAC was unchanged.

4. The data suggest that amygdala kindling produces long lasting catecholaminergic changes in the hypothalamus, a major target for amygdaloid efferent fibers. They are in general agreement with the “noradrenaline hypothesis” of kindling.

1. Mice receiving lithium carbonate (1.5 or 3 mg/ml) in their drinking water for a duration of 7 to 10 days were examined on a battery of psychopharmacological tests.

2. The well-known learned aversion of rats for lithium was confirmed in mice and the increase in body weight was reduced by lithium. These two effects were concentration-dependent.

3. Lithium partly antagonized the hypothermia induced by reserpine, oxotremorine, or a high dose of apomorphine.

4. As this antagonistic effect is also shared by the tricyclic or MAOI antidepressants as well as by beta-adrenergic stimulants, it is suggested that lithium could act as an anti-depressant by increasing the release of noradrenaline.