Progress in neuro-psychopharmacology最新文献

1. In naive male rats morphine sulfate administered intraperitoneally in doses less than 25 mg/kg produced hyperthermia, while higher doses produced hypothermia.

2. In morphine tolerant rats, morphine produced only hyperthermia at all doses with a markedly reduced time of onset.

3. When morphine was acutely administered intravenously, all doses tested (2,5,10 and 20 mg/kg) led to an initial hypothermia; hyperthermia subsequently occurred at doses 2,5 and 10 mg/kg, but not at 20 mg/kg.

4. Naltrexone (5 mg/kg) antagonized both the hyperthermic and hypothermic response to intraperitoneally administered morphine, and when the hypothermic response was antagonized, hyperthermia occurred.

5. Adrenalectomy retarded the hyperthermic effects of intraperitoneally administered morphine in both naive and tolerant subjects.

6. It is suggested that hypothermia is a primary action of morphine on central thermoreceptors, and that certain components of the hyperthermic response are induced indirectly, perhaps through hormones of the adrenal glands.

1. The food and water intake and diuresis of male Sprague-Dawley rats were monitored after a single injection of β-phenylethylamine (PEA), and thereafter, at 7 day intervals during 4 weeks of drug treatment.

2. PEA reduced 24 hour food intake (maximal effect of 20% reduction at 50 mg/kg) after a single injection and tolerance did not develop to this effect during four weeks treatment. Similarly PEA caused a dose dependent reduction in body weight gain during this period.

3. The anorectic effect of PEA appears to be behaviourally specific to feeding since there was no concurrent inhibition of water intake or diuresis.

1. In the last years many studies have demonstrated that the maintenance therapy with depot-neuroleptics could reduce the readmissions of schizophrenic outpatients in comparison to short-acting medication.

2. Most placebo-controlled studies are based on a follow-up of only one or two years. In a “mirror-image” study over 5 years the relapse rates and the duration of the hospital stay of 78 schizophrenic outpatients treated with depot-neuroleptics were compared with these parameters under short-acting medication.

3. There was a high significant reduction of the readmissions rate and of the inpatient time under the treatment with depot-neuroleptics.

4. The demographic data and therapeutic conditions which influence these results were discussed.

1. Various conclusions about the opiate effects in the central nervous system can be drawn from studies involving the recording of nerve impulses (action potentials). There are, for example, regional differences in the kind and character of opiate effects, both in acutely treated animals and during the development of tolerance to repeated exposure to opiates.

2. Generally speaking, opiates depress neuronal activity with pharmacological stereospecificity. Excitatory effects (some of which are stereospecific and due to disinhibition) do occur in several brain regions. Excitatory effects can become more prominent during tolerance development.

3. Opiates interact with major neurotransmitter systems in a variety of ways that include not only post-synaptic agonist/antagonist phenomena but also pre- and post-synaptic modulatory functions; mechanisms of such interactions are poorly understood and are a focus of current research in many laboratories.

4. Opiates have profound effects in various brain structures that are known to be associated with the more prominent behaviors that are induced by opiates, as reflected in such phenomena as catalepsy, euphoria, reward and analgesia. There is, however, no clear understanding or unified theory to explain how these effects are produced. In the case of analgesia, the opiates are known to act simultaneously within nociceptive pathways at several levels: spinal, brainstem, and thalamic.

5. The widespread distribution of cells that are sensitive to both the stereospecific and non-stereospecific effects of opiates makes it likely that the various behavioral effects of opiates are mediated through several receptor types and several levels of the nervous system.

1. We studied L-DOPA, DOPS and tyrosine as precursors of CAs using GC/CI/MS techniques to measure the effects of these amino acids in rats on the production of metabolites in brain and urine.

2. L-DOPA caused a significant increase in levels of brain NE metabolites which was not blocked by the peripheral decarboxylase inhibitor, Ro4-4602.

3. DOPS increased brain levels of both NE and DA metabolites but the increases in NE (but not DA) metabolites were blocked by Ro4-4602.

4. Tyrosine had no significant effect on CA metabolites in brain, but metabolites of tyramine and octopamine were increased 2- to 3-fold.

5. We conclude that interpretation of results obtained with these precursor amino acids may be complicated by their lack of specificity or by conversion to amines in the brain capillaries.

1. Chlorimipramine has been reported to be effective in the treatment of phobic-obsessive patients. It has been widely used in combination with anti-anxiety compounds such as benzodiazepines, or with major tranquillizers, such as butirophenones, but no clear-cut superiority of anyone of these treatments has been yet established.

2. A multicenter trial was performed to compare the therapeutic characteristics of chlorimipramine alone with those displayed in combination with haloperidol or diazepam in patients showing an obsessive and/or phobic sympomatology.

3. A total of 54 inpatients of both sexes were admitted to a 60-day trial and were treated in double-blind conditions. The experiment was carried-out in three groups: chlorimipramine, chlorimipramine and diazepam, and chlorimipramine and haloperidol.

4. The psychopatological picture and the evaluation of clinical efficacy was assessed by a battery of instruments: the MMPI, the RSD of Hamilton, the BPRS of Overall and Gorham and the IMPS of Lorr. For safety a check-list of side-effects has been used.

5. After statistical processing, the data gathered from various centres seem to indicate differentiated types of response in all three treatments. These data suggest a possible differentiation in the use of the three treatments.

1. Animals will work for stimulation of some parts of their own brains; this suggests that the brain has specialized circuitry for mediation of reward.

2. Current evidence identifies two links in such circuitry: a myelinated, descending, medial forebrain bundle link and an ascending, dopaminergic, medial forebrain bundle link. The myelinated link makes probable synaptic contact with the dopaminergic cells of the ventral tegmental area and substantia nigra. These dopaminergic cells may receive other myelinated and reward-relevant afferents as well, particularly from the brainstem.

3. Psychomotor stimulants facilitate intracranial self-stimulation by acting at terminals of the dopaminergic link, particularly in nucleus accumbens. Opiates facilitate self-stimulation by acting at the dopamine cell bodies in the ventral tegmentum. Facilitation of self-stimulation by other drugs of abuse has not been localized to a site of action.

4. Psychomotor stimulants have rewarding actions of their own in nucleus accumbens. Opiates have rewarding actions at the dopaminergic cell body region of the ventral tegmentum. The sites of rewarding action have not been determined for other drugs of abuse.

5. The substrate mediating rewarding actions of opiates and psychomotor stimulants also mediates the rewarding action of more natural rewards like food and water. The fact that some drugs of abuse can come to dominate behavior in relation to more natural rewards may stem from the more direct central actions of drugs on the reward substrate. The fact that the rewarding effects of food, water, opiates, and psychomotor stimulants feel subjectively dissimilar may simply reflect the fact that while a common rewarding action is shared by these agents, many other effects which are subjectively experienced differ between agents and obscure awareness of a common dimension of all positive rewards.

1. Measurements of CSF GABA levels were performed on different groups of psychiatric patients.

2. Two different methods were used for determination of CSF GABA concentration: a) gaschromatography/ mass spectrometry and b) amino acid analysis with fluorescence detection.

3. No difference in CSF GABA levels between control patients and untreated schizophrenic patients was seen.

4. An increase of CSF GABA levels was found after 30 days of treatment with sulpiride and during chronic treatment with different neuroleptics for many years in long-stay hospitalized schizophrenic patients.

5. In short-stay hospitalized schizophrenic patients after a period of about 6 weeks of treatment with different neuroleptics in combination with benzodiazepines and antiparkinsonian drugs a decrease of CSF GABA levels compared with control patients was observed.

6. It is assumed that the increase of GABA in CSF could be indicative for a neuroleptic drug. The simultaneous administration of benzodiazepines and antiparkinsonian drugs might be responsible for the decrease in CSF GABA levels.

1. Information exchange positively influences the development of this important branch of biomedical research.

2. WHO, with its Collaborating Centres on Psychopharmacology, has made certain steps towards the improvement of information exchange in psychopharmacology on an international level.

3. Several collaborative activities are devoted to the different aspects of modern psychopharmacology for meeting countries' needs, especially those of developing countries. Exchange of information forms an essential part of these activities.