Psychopharmacology communications最新文献

Three selected members of a stable juvenile primate social colony of six, peer-raised, one-year old Stumptail macaques received 0.5 mq/kg of d-amphetamine sulfate daily for four weeks. Amphetamine significantly reduced play activity to a minimum in the treated monkeys throughout the treatment period. These animals preferred huddling with eyes open, although no sedation was apparent. As the treatment period progressed, stereotyped behavior developed, rising significantly during the final week of treatment. This model may be useful in studying the seemingly "paradoxical" quietening effect of amphetamine in children.

While the 5-HT precursors tryptophan and 1-5-HTP cause an increase in serum prolactin concentration, a combination of 1-5-HTP with a peripheral decarboxylase inhibitor was found to reduce the serum prolactin concentration. This combination seemed to behave like a DA agonist. This effect is not produced by the decarboxylase inhibitor per se. A possible explanation is that 5-HTP is converted to 5-HT in CA-ergic neurons, that 5-HT supersedes the CA from the stores, and that some of the CA reach the synaptic cleft and stimulate CA receptors. Another possible explanation is that 5-HTP decarboxylase is centrally inhibited as well, and that an effect of 5-HTP itself is involved here. In view of the observations made it is doubtful whether the therapeutic effect of 5-HTP combined with a peripheral decarboxylase inhibitor in depressions and myoclonus can in fact be atributed to activation of central serotonergic systems.

A recent study suggested that low plasma levels (58-70 ng/ml) of chlorpromazine (CPZ) were achieved by patients concurrently taking lithium, despite ingestion of doses of CPZ (400-1000 MG) which ordinarily produce plasma levels of 100-300 ng/ml or more. We have studied this lithium-chlorpromazine interaction in rats. The plasma and brain levels of [14C]chlorpromazine (CPZ) after an oral dose (5 muCi) were significantly lower (p less than 0.005) in rats treated with lithium, whereas the percent of dose remaining in the stomach (24-30%) was significantly higher (p less than 0.001), than in matched controls. Gastric emptying was measured by [14C]polyethylene glycol and was shown to be inhibited significantly by oral and i.p. lithium. This inhibition of gastric emptying by lithium may be the major cause of the lower plasma levels of CPZ since diminution of plasma drug levels has been shown for L-dopa, chlorpromazine, sulfa drugs, and phenylbutazone in animals and man treated concomitantly with anticholinergics, which also diminish gastric motility.

The effect of chlorothiazide on the pharmacokinetics of lithium in both plasma and RBCs was studied in normal adult males. This was accomplished by administering single, 300 mg. doses of lithium carbonate alone and concurrently with chlorothiazide (0.5 grams/day for one week). Thiazide administration resulted in increases in plasma and RBC concentrations of 26.2 and 25.4%, respectively, as well as a 26.5% decrease in renal lithium clearance. The data were analyzed in terms of a two compartment pharmacokinetic model as previously reported (8). The results of this analysis showed that the change in renal lithium clearance could be accounted for by a 24.1% reduction in the value of ke, the excretion rate constant. It was also shown that changes in plasma lithium concentration during chronic lithium therapy would be expected to increase by 25-30% when chlorothiazide therapy is employed. The model also predicts that changes in RBC concentrations would parallel those occurring in plasma and thus no change in the RBC/plasma lithium ratio would be expected.

Systemic administration of lysergic acid diethylamide (LSD) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of increased activation of central serotonin receptors. Utilizing this behavioral measure, a marked supersensitivity to LSD was observed in rats whose serotonin nerve terminals had been selectively destroyed, and a dramatic tolerance to LSD was observed following its repeated administration to normal rats. These data provide direct evidence that LSD can stimulate CNS serotonin receptors to a degree which markedly affects behavior.

Free and conjugated lumbar cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured before and after probenecid treatment in 12 schizophrenic patients by a gas liquid chromatography-mass fragmentographic procedure. Neither the free nor conjugated MHPG was appreciably altered by probenecid. Total MHPG was statistically increased by probenecid but not to the point that the probenecid test would be clinically useful for estimating norepinephrine turnover from probenecid-induced changes in MHPG concentrations.

Inbred mouse strains exhibit differences in motor activity and brain catecholamine metabolism after acute morphine injection. The two strains C57BL/6J and Balb/cJ, which increased motor activity after morphine present also an increased noradrenaline turnover in the pons medulla, whereas no difference were found in the DBA/2J strain whose motor activity was unchanged. A correlation seems to exist between motor activity and the noradrenaline metabolism in the brain stem.