Psychopharmacologia最新文献

Twelve healthy volunteers were given butobarbitone 100 and 200 mg, nitrazepam 5 and 10 mg and 2 lactose dummy treatments, at 23.00 hours at weekly intervals over 6 weeks according to a balanced design and using double blind conditions. Performance was studied between 09.00 hours and 17.00 hours the following day. Significant (P is less than 0.05) impairment of tapping rate and digit symbol substitution occurred. No significant differences occurred between performance after active drug and dummy in auditory vigilance, and subjective effects. Examination of individual differences in the response of subjects to the 4 hypnotic drug treatments, compared with their responses after dummy, indicated that subjects could be divided into two groups. One group consistently rated themselved as more alert after hypnotics and their vigilance performance improved. The other group consistently were more drowsy after hypnotics and their performance was impaired. It is suggested that the improvement in the first group resulted from improved sleep quality sufficient to counteract the residual effect of the hypnotic, whereas the second group merely showed the residual effects of the drugs.

In healthy volunteers the emetic effect of apomorphine (5-10 mg, i.m.) was prevented by haloperidol (2 mg), metoclopramide (10 mg) and sulpiride (100 mg), injected intramuscularly. In parkinsonian patients, apomorphine (1 mg) given alone ameliorated the neurological symptoms (30% improvement in the disability score), but the improvement was accompanied by nausea, vomiting, sedation or sleepiness. Haloperidol (2 mg) prevented not only the emetic effect of apomorphine (10 mg), but also its therapeutic efficacy in parkinsonism. Indeed, the disability score was worsened by the drug combination in some patients. Moreover, after haloperidol, apomorphine produced deep sedation and sleep. By contrast, in parkinsonian patients pretreated with metoclopramide (10 mg) or sulpiride (100 mg), apomorphine (10 mg) markedly diminished tremor and rigidity and failed to produce nausea, vomiting and sleepiness.

Rats were allowed to self-administer a solution of 0.9% saline, or 0.01, 0.03, 0.1 or 0.3 mg/kg/infusion of methadone hydrochloride or 0.03, 0.1 or 0.3 mg/kg/infusion of morphine sulfate. The results showed that number of infusions taken was an inverse function of unit dose, while amount of drug self-administered (mg/kg) was a direct function of unit dose. The data also indicated that more morphine than methadone was self-administered.

Sixteen adult males participated in a repeated measures design in which they served as their own control to determine the effects of various amounts of alcohol on: (1) their sexual arousal elicited by erotic motion-pictures, as measured by a penile transducer, (2) the ability to voluntarily inhibit their arousal to those same films in accordance with instructions, and (3) the ability to become voluntarily aroused in the absence of overt stimuli. The ingestion of a low (0.5 or 0.6 ml/kg) or a moderate (1.0 or 1.2 ml/kg) amount of alcohol resulted in a small, but significant, depression of mean sexual arousal, but other measures were not affected. However, the ingestion of a high (1.5 or 1.8 ml/kg) amount of alcohol resulted in every measure of evoked arousal being depressed by a comparatively large degree. The high level of alcohol also affected a very large decrease in sexual arousal when subjects were instructed to become sexually aroused in the absence of overt erotic stimuli. In contrast, none of the three amounts of alcohol caused a significant impairment in the ability of subjects to voluntarily inhibit their sexual arousal, even though most subjects experienced some deterioration in that ability after ingesting a moderate amount of alcohol. The actions of alcohol on sexual responses were not significantly correlated with its effects on a nonsexual matching task, were not related to subjective reports of how alcohol usually affects sexual behavior, and were generally not related to reported drinking history.

The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively.

Male and female rats received during infancy either handling or injections of saline, phenobarbital, haloperidol, diazepam, chlorpromazine, and amphetamine. On reaching adulthood, the behavior of these animals was measured in an open-field arena and in a Lashley III maze. Saline injections per se affected the behavior of males but were unable to change that of females. The drugs provoked increased ambulation and/or decreased defecation of males in the open field, whereas with the females the opposite was observed, that is, a decreased ambulation and/or an increased defecation. Consequently, the early drug treatments abolished the sexual differences normally observed in ambulation and defecation of rats. Four of the 5 drugs tested deteriorated the maze performance of both male and female rats.

A series of experiments was designed to assess the effect of physostigmine on the retention of an appetitively-reinforced Y-maze discrimination. The results supported in part the model of cholinergic involvement in long-term memory as proposed by Deutsch, in that physostigmine respectively impaired and enhanced well-remembered and poorly-remembered responses. However a modification of the model was presented to accommodate futher findings that variations in both dose-level of administered physostigmine and initial leraning ability influenced subsequent retention, depending on the training-testing interval.

Rats were trained to press a lever in order to stimulate their hypothalamus through a chronically implanted electrode. Dose-response curves were determined for the effects of morphine (0.3-10 mg/kg), pentazocine (1.0-30 mg/kg), cyclazocine (0.03-30 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) on responding for intracranial stimulation, and then were redetermined in the presence of one or two doses of naloxone. The three analgesics produced only dose-related decreases in responding with the following relative potencies: cyclazocine greater than morphine greater than pentazocine. The well-documented rate-increasing effects of d-amphetamine on intracranial self-stimulation were observed at 0.3 and 1.0 mg/kg of the drug; decreases in responding at 3.0 mg/kg were associated with stereotyped behavior. Naloxone, which had no effect of its own on self-stimulation, increased the dose of the analgesics required to depress response rate in a manner consistent with a competitive antagonism. In contrast, response rates at all doses of d-amphetamine tested in the presence of naloxone. Thus, the interaction between naloxone and d-amphetamine is qualitatively different from the one between naloxone and the analgesics. This finding extends to intracranial self-stimulation the generality of a previous report of interactions between d-amphetamine and naloxone on behavior in the rat.

This study was designed to examine the hypothesis that phenelzine is metabolized by polymorphic acetylation and that its effects are dependent on acetylator status. 30 depressed inpatients were given a 3-week course of phenelzine 30 mg t.i.d. The antidepressant effect, the degree of inhibition of monoamine oxidase and the amount of free phenelzine excreted in the urine were all significantly greater in slow acetylators than in fast. These findings strongly support the hypothesis.

The effect of chronic consumption of alcohol on the circadian variations of the plasma corticosterone investigated in DBA/2J male mice. After 15 weeks of alcohol consumption (3.8%w/v for the first week and 7.5% for subsequent weeks) the alcohol groups exhibited a flattened circadian corticosterone curve, the level being intermediate between the peak and trough values of the water control groups. The diurnal patterns of food and liquid consumption were still present at the 10th week of alcohol treatment in the alcohol groups, although the absolute amount of food and liquid consumed at each of the 6-h intervals was somewhat different between the alcohol and water groups. The blood alcohol showed a peak at early morning with the mean of 100 mg/100 ml, but the levels of alcohol during the remaining periods were remarkably stable, the means ranging from 30 to 46 mg/100 ml. Chronic consumption of alcohol, even relatively low concentrations, appears to affect the neural sites in the CNS controlling the circadian rhythm of ACTH release.