Progress in neuro-psychopharmacology最新文献

1. The neuro- and cardiovascular effects of RS-51324 (DL-4(5)-(2,6dichlorophenyl)-2-methoxycarbonyl-amino-4,5 dihydroimidazole) have been explored in animals.

2. Antidepressant activities of RS-51324 were demonstrated by reserpine antagonism and L-DOPA potentiation.

3. Norepinephrine uptake was inhibited but MAO activity was not inhibited by RS-51324.

4. Peripheral vascular responses to serotonin were potentiated although central effects were not demonstrated.

5. Cardiovascular experiments indicated that RS-51324 lacked anticholinergic effects but had mild antihistaminic activity.

6. RS-51324 potentiated tyramine-induced pressor responses.

7. RS-51324 lacks centrally acting skeletal muscle relaxant activity.

8. The LD₅₀ of RS-51324 was greater than 2 gm/kg.

9. RS-51324 appears to be a membrane-pump inhibiting compound with probable antidepressant activity.

1. Animals exposed to inescapable stress display avoidance and escape deficits when tested in a later task situation where successful responding results in stress offset, a phenomenon termed learned helplessness. This paradigm has been suggested as an animal model of depression as it shares many of the characteristics of the human disorder.

2. An escape delay procedure previously shown to reveal interference effects in mice was reproduced in rats.

3. Using this escape delay procedure, the effects of acute and sub-acute administration of nortriptyline on learned helplessness behavior were assessed.

4. Four and 6 days of drug treatment reversed the escape deficits produced in animals exposed to pre-shock whereas the 0 and 2 day drug regimens were without effect.

5. These findings support the utility of the learned helplessness model in evaluating the potential of antidepressant agents in experimental animals.

1) Two groups of rats were trained to jump a hurdle in order to avoid the intravenous infusion of either 800 mg/kg ethanol or saline.

2) In Phase I, with the hurdle height fixed at 9″, none of the animals acquired the avoidance response. In Phase II, where the hurdle height was slowly increased from 1″ to a maximum of 10″, all of the animals receiving ethanol but none of the animals receiving saline acquired the avoidance response.

3) This finding suggests that some properties of ethanol are aversive and can motivate the acquisition of an active avoidance response.

1. The microassay method of Taylor and Snyder for determining the activity of histamine N-methyltransferase (E.C.2.1.1.8) (HMT), the histamine metabolizing enzyme, was modifies to permit the simultaneous measurement of histamine and HMT activity in the same tissue sample under our experimental conditions.

2. The synthesis and purification of τ-methyl-[¹⁴C]-histamine was performed to assess the efficiency of extraction of methylhistamine which in this modified methodology is approximately 80 percent.

3. The influence of ethanol, acetaldehyde, morphine and naloxone alone and in combination on hypothalamic, thalamus-midbrain and cerebral cortical HMT activity was investigated at concentrations of 0.1 μM to 500 μM.

4. Ethanol, acetaldehyde and ethanol in the presence of 1 μM morphine failed to markedly influence HMT activity.

5. At high concentrations morphine strongly inhibited while naloxone enhanced enzyme activity. Morphine's effects on HMT remained unaltered by 1 μM naloxone.

6. In the present study low concentrations of ethanol and morphine have little effect on HMT activity ‘in vitro’. These observations suggest that changes in HMT activity may play a minor role in the alcohol and morphine-induced central histamine changes observed in our previous ‘in vivo’ studies.

1. Reported changes in neurotransmitter systems with aging in human and animal brain are briefly reviewed. The effects of age appear to vary from region to region in brain, as well as from system to system. Considerable evidence is available that dopaminergic activity decreases with age, particularly in the striatum and nucleus accumbens; this loss may be important to age-related losses in agility and increases in the incidence and severity of tardive dyskinesia. Lesser, but still convincing, evidence indicates decreases with age in noradrenergic, GABAergic and cholinergic systems, with the most marked effects being found, respectively, in the hypothalamus, thalamus and cortex-hippocampus. The cortical and hippocampal losses in cholinergic activity are markedly accentuated in senile dementia of the Alzheimer type and are probably related to memory defects in aging and dementia.

2. Serotonin and met-enkephalin systems in the hypothalamus are probably relatively unchanged by age and little or no information is available on numerous other putative transmitters.

3. Brief consideration is also given to age-related changes in the density of specific binding sites, possible reasons for lack of therapeutic effect of choline analogs in senile dementia, and the question of whether cell death, loss of nerve endings and/or decreased neuronal vitality underlie the deficits found.

1. This paper attempts to provide an overview of our research which has led us to the concept of tolerance as adaptation to drug effects rather than adaptation to the drug itself.

2. This notion can be expanded to include drug tolerance as an example of a range of adaptive manifestations of neuroplasticity.

3. The suggestion that serotonin (5-HT) is involved in general adaptive processes gave impetus to exploration of its role in tolerance.

4. The paper focusses, therefore, primarily on the line of research that started with whole brain manipulation of brain 5-HT and evolved into a study of the effects of discrete and localized depletion of 5-HT.

5. The evidence for the role of median raphe nucleus, the limbic 5-HT, central norepinephrine (NE), and Des-Gly⁹ (Arg⁸) vasopressin (DGAVP) in ethanol tolerance is also provided, with the relationship between the median raphe nuclei and the limbic system most clearly delineated.

1. Male hooded rats were trained to discriminate the anxiogenic action of phentylenetetrazol by responding for food reinforcement with a lever located on one side of a food cup 15 min following a 20 mg/kg pentylenetetrazol injection and responding with the lever located on the alternate side of the food cup 15 min following a 1 ml/kg saline injection.

2. Cocaine (20 mg/kg) but not diazepam (5 mg/kg) nor haloperidol (0.16 or 0.64 mg/kg) significantly generalized to the pentylenetrazol discriminative stimulus.

3. Diazepam (5 mg/kg) but not haloperidol (0.16 or 0.64 mg/kg) significantly antagonized the discriminative stimuli produced by pentylenetetrazol and cocaine.

4. These data suggest that cocaine produces discriminative stimulus that is related to its anxiogenic action.

1. The number of psychotropic drugs and the literature on them is rising from year to year. The publications from the International Reference Center for Psychotropic Drugs (Psychopharmacology Bulletin, Psychotropic Drug Index and Mental Health Literature) help to codify this stream of information.

2. The Committee for the Prophylaxis and Therapy of Depressions founded in 1975 aims at keeping physicians outside psychiatry up-to-date with the pharmacotherapy and clinical picture of depressions. The fact that the Psychiatric University Clinic of Basle combines the activities of the Committee with those of a Regional Reference Center is very favourable as the two organizations are complementary.

1. The piperazine derivative, piribedil (ET495), in doses ranging from 10 to 100 mg/kg reduced locomotor activity and exploration in rats naive to the holeboard, but had less effect on exploration and was without effect on locomotor activity in rats familiar with the apparatus.

2. Doses of 5–100 mg/kg disrupted the usual between-day decrement in exploration and locomotor activity, but did not change the increase in head-dipping when novel objects were introduced on the second day.

3. ET495 and amphetamine counteracted each other's effects on locomotor activity, but had similar and additive effects on exploration.

4. Haloperidol did not antagonise the effects of ET495.

5. ET495 (0.5 & 1 mg/kg) increased social interaction between male rats when they were tested in an unfamiliar arena, but was without effect in a familiar one.

6. The effects of ET495 are dependent on the animal's familiarity with the test arena, but over the dose-range tested (0.5 to 100 mg/kg) there was no evidence of low doses acting on presynaptic receptors to produce stimulation of locomotor activity or exploration. The enhanced social interaction found after low doses might reflect a presynaptic action.