Psychopharmacologia最新文献

Three dose levels, 0.2, 0.4, and 0.6 mg/kg, of delta9-tetrahydrocannabinol (THC) and a placebo were orally administered to 10 frequent and 10 occasional marijuana users. Following ingestion of each dose and the placebo, objective tests selected from a battery of sensory and perceptual motor tests routinely used to evaluate cerebral dysfunction in hospitalized patients were administered. The influence of delta9-THC on proficiency and variability of performance was minimal. However, when individual test scores and variabilities were combined and converted to standard scores, allowing for analysis of overall performance, THC had a small but consistent detrimental effect on both proficiency and variability of performance. In contrast, THC exerted profound effects on the subjective experiences of the volunteers as assessed by the Subjective Drug Effects Questionnaire. Subjective changes in mood, feeling, perception and somatic sensations were reported by all subjects but were more pronounced in the occasional user group. It was proposed that the small impairment noted in objective test performance after ingestion of delta9-THC as contrasted to the large effects on subjective responses suggests that the principal effects of marijuana are on the autonomic nervous system rather than on higher cortical functions.

The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergic-cholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug.

The effects of ethanol and isopropanol were studied on responding by pigeons under multiple fixed-ratio (FR), fixed-interval (FI) schedules of food presentation and under a fixed-interval (FI) schedule of food presentation where responding was decreased by punishment. The ethanol was rapidly absorbed into blood and decreased responding within 15 min after intubation to the opening of the proventriculus. Dose-effect determinations of the effects of ethanol showed that ethanol decreased responding in both the FR and FI components of the multiple schedules at similar doses, but there were increases in responding under an FR 100 schedule at lower doses. Isopropanol tended to decrease FR responding at doses that either increased FI responding or did not affect FI responding. Both ethanol and isopropanol (1 g/kg) produced effects on the local rates of responding within the FI which were rate-dependent in that they increased low rates while not affecting or actually decreasing the high rates of responding. Both ethanol and isopropanol increased punished responding if it was not severely suppressed by the punishment procedures.

This experiment was done to test the prediction that preexposure to a drug state would increase the discriminability of that drug state when used as a cue in a discrimination task. Eight rats were pre-exposed to scopolamine for 20 days and 8 rats were given saline injections. The drug pre-exposed animals acquired a drug state discrimination more quickly than the controls. A difference was also found between the generalization gradients for each group with the pre-exposed group showing a steeper generalization gradient.

The effects of chlorpromazine on the acquisition of a brightness discrimination with food reward were examined. Doses of 0.5, 1.0 or 2.0 mg/kg of CPZ as well as saline were administered intraperitoneally to 4 groups of 7 Sprague-Dawley rats, 1 h prior to testing. After a 3-week period of habituation and pre-training, rats were tested 20 trials a day, 7 days a week. No drug effect was found on the number of trials to reach a criterion of 18/20 successive correct responses, which required an average of 6.2 days of training. Precriterion latencies, however, showed an increase as a function of increasing dose level. Post-choice latencies were not affected, eliminating motor retardation as an explanation for the latency effect.

Coffee-drinking cigarette smokers take in more nicotine when they ingest almost no caffeine than when they ingest an amount of caffeine ranging from 75 mg to 300 mg. They do not take in relatively less nicotine as the dose of caffeine increases from 75 mg to 300 mg. It seems, then, that something due to caffeine deficit is responsible for the effect. Heavier users of caffeine show this effect less strongly than do lighter users of caffeine. These results are discussed in terms of the discriminability of caffeine and nicotine deficits and the possible influence of differential tolerance to caffeine. The importance of evaluating caffeine consumption when studying nicotine use and the importance of considering the chronic level and use of these drugs when studying their effects on behavior is indicated.

The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug.

Ergometrine (8 mg/kg) injected intraperitoneally into normal rats had little effect on locomotor activity. In contrast, rats with selective 6-hydroxydopamine-induced lesions of dopamine terminals in the nucleus accumbens showed a strong stimulation of locomotor activity following injection of this dose or ergometrine. The dopamine analogue 2-amino-6-7-dihydroxy-1, 2, 3, 4-tetrahydronaphthalene (ADTN) (150 mug), caused strong and long lasting stimulation of locomotor activity when injected intracerebroventricularly into rats. The ADTN response was markedly reduced in rats with bilateral electrolytic lesions of the nucleus accumbens, but unchanged in rats with bilateral electrolytic lesions of the caudate nucleus. At a lower dose level (50 mug) ADTN, injected intracerebroventricularly, had little effect on the locomotor activity of normal or sham-operated rats. This dose of ADTN was, however, effective in causing locomotor stimulation of rats with bilateral 6-hydroxydopamine-induced lesions of the nucleus accumbens. These results support the view that the dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs.

The neuroendocrine effects of haloperidol, usually reported as side effects of this drug when given in antipsychotic doses, have not been systematically investigated. In the present study five normal adult men were administered saline and two doses of of haloperidol (0.25 mg, 0.5 mg) intramuscularly in a double-blind randomized block design. The anterior pituitary hormones GH, LH, FSH, and PRL were measured in blood samples taken every 20 min for several hours thereafter. The low doses of haloperidol used have been shown by others to alter the human EEG; in our subjects these doses produced no objective or subjective clinical effects. There were no drug related changes in GH, LH, or FSH. PRL, however, showed a prompt, statistically significant, dose-related increase in plasma levels, with a return to baseline with 5 h. Haloperidol has strong dopamine-blocking effects, and the hypothalamic inhibitory mechanism for PRL release is believed to be dopamine-mediated. The results of this study suggest that haloperidol may have utility in low doses primarily for its hypothalamic neuroendocrine effects, and that dose-related PRL release may be a useful paradigm for comparing dopamine-blocking antipsychotic agents in humans.

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.