Progress in neuro-psychopharmacology最新文献

1. All of the most commonly used antianxiety drugs (benzodiazepines, barbiturates, ethanol) selectively enhance GABA-mediated neurotransmission.

2. The degree of GABA-potentiation produced by benzodiazepines correlates well with their relative affinities for the benzodiazepine receptor.

3. Repetitive stimulation of the recurrent inhibitory GABAergic pathway in rat hippocampus leads to a remarkable reduction of the effectiveness of GABA; this “disinhibition” is counteracted by antianxiety drugs.

4. A neurophysiological model is proposed, conceptualizing anxiety as the by-product of hypervigilance occurring in frequencies higher than those that the GABAergic system can accommodate, before “fading” or “desensitization” occurs.

1. Rats were rendered dependent on diazepam by administrating escalating dosages of diazepam in diet.

2. At the time of diazepam withdrawal, the animals were treated with parachlorophenylalanine (PCPA), a potent serotonin (5-HT) depleter, or the corresponding vehicle.

3. After diazepam withdrawal, PCPA-treated animals showed abnormal behaviors, such as aggression, irritability, vocalization and muscular rigidity.

4. In contrast, little or no changes in behavior were observed in control animals.

5. These results suggest that depletion of brain 5-HT by PCPA potentiates diazepam withdrawal signs.

1. This study compares brain levels of acetylcholine (ACh) and choline, and ACh brain turnover in 3 inbred strains of mice, CF-1, C57B1/6 By and Balb-c-By; these parameters were measured in control (aggregated) mice as well as following two paradigms, mild footshock and isolation, applied alone or in combination.

2. Enzymic radioassay method was used to measure brain ACh and choline; ACh turnover was evaluated by two computation methods.

3. Aggregated Balb-c-By mice exhibited low ACh and choline levels as compared to those of the mice of the two other strains. ACh levels of C57B1/6 By and CF-1 mice did not differ significantly; choline levels of CF-1 mice were almost twofold higher than those of C57B1/6 By mice.

4. ACh turnover of aggregated CF-1 mice was about twice as high as that of C57B1/6 By and more than twice higher than that of Balb-c-By mice.

5. The effects of shock, isolation, or shock combined with isolation on the brain levels of ACh and choline of mice of the 3 strains were inconsistent and, frequently absent.

6. ACh turnover was significantly decreased in the brains of CF-1 by the two paradigms, whether employed alone or in combination; there was no additive effect when footshock was combined with isolation.

7. ACh turnover did not change consistently after the two paradigms, employed alone or in combination, in the case of C57B1/6 By and Balb-c-By mice; in some cases, ACh turnover was increased.

8. Footshock proved to be a mild inducer of aggression as compared to isolation in the 3 mice strains; footshock combined with isolation proved to synergize with respect to aggression in the 3 strains. Whether exposed to footshock and isolation alone or to the combination of these procedures, CF-1 mice were significantly more aggressive than Balb-c-By and C57B1/6 By mice.

9. It is emphasized that consistent facilitatory effect of the two paradigms on aggression as well as additive effect on aggression resulting from combining footshock and isolation should be contrasted with the inconsistent effects of the two paradigms, applied alone or in isolation, on ACh turnover; altogether, the data did not indicate that aggression is related to increased brain ACh turnover.

1. Adult female outbred cats were prepared with chronic hypothalamic stimulating electrodes and ventricular cannulae.

2. Cats were restrained, and patterned aggressive reflexes of elicited head turning, biting, and paw striking to proximate stimulation were assessed under a variety of stimulation conditions.

3. In comparison with vehicle injection cholinergic stimulation by arecoline facilitated the three reflexes and cholinergic blockade by scopolamine inhibited them.

4. Cholinergic-muscarinic receptors may be involved as mediators of terminal (consummatory) behaviors in aggressive syndromes.

1. The Continuous Performance Task (CPT), widely regarded as a test of attention span, has become extensively used in psychopharmacological research.

2. A system for regulation of the CPT and other experimenter paced tasks is described. This control unit provides a cheap, reliable, and portable means for conducting such tests without expensive laboratory equipment.

3. Suggestions are offered concerning other aspects of the system, including the production of control tapes, presentation of stimuli, data output, and recommended time parameters.

1. The charts of 46 bipolar manic-depressive and schizo-affective patients who were on lithium carbonate for more than 2 years were carefully reviewed.

2. Age of onset, age of lithium initiation, sex, family history of affective disorder and diagnosis were not related to lithium response.

3. Poor lithium response was associated with a higher frequency of episodes.

4. Fair lithium response was associated with a mean lithium level below 0.7 mEq/L.

1. Bupropion HCI (Wellbutrin^®), a new antidepressant, has been reported to have low cardiovascular toxicity as a result of its specific inhibiting effect on the re-uptake of dopamine.

2. In order to investigate its effect on the cardiovascular system we administered bupropion for two weeks to 5 depressed patients who manifested clinically significant orthostatic hypotension while being treated with tricyclic antidepressants. Treatment with bupropion was preceded by one week of placebo washout.

3. Curing bupropion treatment none of the patients manifested significant orthostatic hypotension: in the 4 patients who completed the study the mean difference between supine and standing systolic blood pressure after 14 days of bupropion treatment (8.3 ± 2.5 mm Hg) was the same as after 7 days of placebo treatment (8.3 ± 3.2 mm Hg) and significantly (p < .001) lower than during treatment with tricyclics (22.3 ± 1.4 mm Hg).

4. Thus, buproprion appears to have the advantage that it does not induce orthostatic hypotension, which is potentially important in the treatment of the elderly and those with cardiovascular disease.

1. The effect of methylphenidate on motor activity was studied on chronic schizophrenics with a history of two or more years of neuroleptic treatment.

2. Clinical examination and polygraphic recording - (EEG, EOG and multichannel EMG) were carried out on 41 patients. Of these, 15 had tardive dyskinesia, 11 had minor dyskinetic phenomena and 15 had no clinical signs of hyperkinetic motor disorder.

3. A distinct qualitative pattern of motor activity was observed in TD patients as pseudorhythmic bursts of muscle action potentials which appeared in varying muscle groups at the rate of 0.6 - 1.2/second. These bursts of muscle activity were not found in the non-TD group of patients.

4. Ritalin administration had a marked effect on TD patients as observed by the increased amplitude, duration and distribution of pseudorhythmic bursts. Eight out of 11 patients, with minor dyskinetic manifestations responded to methylphenidate with the same pattern as TD.

5. Methylphenidate was found to evoke and enhance abnormal muscle activity in patients whose extrapyramidal motor system is already affected by neuroleptics. These findings suggest that methylphenidate administration, in combination with polygraphic recordings, may be a useful tool in the early diagnosis of TD.

1. Blood samples were collected from 71 subjects between thirty-six weeks gestation and six weeks postpartum. Sample collection was carried out over a ten-month period. Subjects entered the study in three phases, month of parturition being July-September, October-December, or January-April. Data from each group and each sampling point relative to parturition were analysed separately.

2. Seasonal variation in total tryptophan concentration was noted at six weeks postpartum, when women giving birth between January and April exhibited higher plasma levels than those in the other two groups.

3. Percent unbound tryptophan was highest in women giving birth between July and September, and lowest for the January to April group. This seasonal effect was highly significant from thirty-six weeks gestation to day two postpartum, had disappeared by day five postpartum and reappeared at six weeks postpartum. Plasma concentrations of unbound tryptophan changed in parallel with percent unbound tryptophan. There is some evidence for a partial dependence of plasma unbound tryptophan on environmental temperature.

1. The specific binding of [³H]desipramine to membranes from rat brain cortex is biphasic and the Scatchard analysis of data shows two distinct components: the high affinity component, with a dissociation constant (K_D) of 4.5 nM and the low affinity component (K_D = 80 nM).

2. Different order of potency in displacing the high affinity [³H]desipramine and [³H]imipramine binding was shown by various compounds tested. Nortriptyline and nisoxetine were the most potent displacers of [³H]desipramine specific binding while chlorimipramine and fluoxetine showed highest potency in competing for [³H]imipramine binding sites.

3. Significant correlation was found between the ability of various drugs to inhibit [³H]desipramine binding and their potency to block the neuronal uptake of noradrenaline in brain.

4. The results suggest that the high affinity binding of [³H]desipramine is distinct from that of [³H]imipramine and is most likely associated with sites involved in neuronal uptake of noradrenaline.