PhysEmp :: Medicine :: Pharmacology :: Psychopharmacology

PubMed: 0278-5846

Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats.
Durkin S, Prendergast A, Harkin A Related Articles Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Sep 13; Authors: Durkin S, Prendergast A, Harkin A Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern associated with recreational use of the substituted amphetamine 3,4 methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic considering that psychiatric disorders such as depression and anxiety and responses to first line treatments for these disorders are associated with 5-HT. In this study the effects of prior exposure to MDMA on behavioural and central neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and antidepressant fluoxetine were examined in rats. Animals were administered MDMA (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine treatment groups received either acute (saline injections for 20 days followed by 3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) drug administration. Prior exposure to MDMA resulted in an attenuation of fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); a behavioural test of antidepressant action. In parallel MDMA treatment resulted in significant regional depletions of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [(3)H] paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss was enhanced in animals following chronic fluoxetine administration. Elimination of fluoxetine and its metabolite norfluoxetine from the brain abolished this interaction between MDMA and fluoxetine treatment. Fluoxetine administration reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in animals pre-treated with MDMA. Overall the results show that MDMA induces long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These results have potential clinical relevance, suggesting that 5-HT re-uptake inhibitors such as fluoxetine may be less effective at treating depression in chronic abusers of MDMA. PMID: 18824064 [PubMed - as supplied by publisher]
Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia.
Petronijević ND, Radonjić NV, Ivković MD, Marinković D, Piperski VD, Duričić BM, Paunović VR Related Articles Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Sep 15; Authors: Petronijević ND, Radonjić NV, Ivković MD, Marinković D, Piperski VD, Duričić BM, Paunović VR High levels of homocysteine (Hcy) were suggested to contribute to the pathogenesis of schizophrenia. Recent investigations have shown that treatment with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels while concomitantly reducing the score of positive and negative symptoms in schizophrenic patients. In addition to the availability of nutrients (mainly folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex metabolic regulation that could be disrupted in schizophrenia. This study was designed to test the influence of disease activity on plasma Hcy levels. Plasma Hcy concentrations were measured in male chronic schizophrenic patients with a predominantly positive (SCH (+)) or predominantly negative (SCH (-)) syndrome in schizophrenia immediately upon admission to the hospital (exacerbation phase) and one month later (remission phase). During this period patients received antipsychotic medications without vitamin therapy. The effects of age, duration of illness, folate and B12 concentrations, as well as smoking and coffee consumption habits on the observed changes were evaluated. Age- and sex-matched subjects were included in the control group. In the control group plasma Hcy concentration was 8.75+/-1.84 mumol/L. In the exacerbation phase plasma Hcy concentrations were significantly increased both in SCH (+) (14.91+/-6.19 mumol/L) and SCH (-) groups (12.8+/-3.27 mumol/L). There was no difference in plasma Hcy concentrations between SCH (+) and SCH (-) patients. Serum folate and B12 concentrations were not significantly different in any of the investigated groups of subjects. The plasma Hcy concentrations could not be correlated with age, duration of illness, the score of positive symptoms or the concentration of folate and vitamin B12. A positive correlation was found between plasma Hcy level and score of negative symptoms in both groups of patients. No correlation was found between smoking or coffee consumption habits and plasma Hcy concentrations. All patients exhibited decreased plasma Hcy levels in the remission phase of the illness, with a mean decrease of 2.68+/-1.57 mumol/L. Folate and B12 levels did not differ in the exacerbation and remission phases of the illness. The significant decrease of plasma Hcy levels, without changes in folate and vitamin B12 concentrations in the remission phase of schizophrenia, could indicate an influence of a pathogenetic process involved in schizophrenia on Hcy metabolism. PMID: 18824063 [PubMed - as supplied by publisher]
Mild cognitive impairment presenting with delusional misidentification: A case report.
Wang SC, Tzeng NS Related Articles Mild cognitive impairment presenting with delusional misidentification: A case report. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Sep 13; Authors: Wang SC, Tzeng NS PMID: 18824062 [PubMed - as supplied by publisher]
Lithium as a treatment of clozapine-induced neutropenia: A case report.
Brunoni AR, Kobuti Ferreira LR, Gallucci-Neto J, Elkis H, Velloso ED, Vinicius Zanetti M Related Articles Lithium as a treatment of clozapine-induced neutropenia: A case report. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Sep 12; Authors: Brunoni AR, Kobuti Ferreira LR, Gallucci-Neto J, Elkis H, Velloso ED, Vinicius Zanetti M PMID: 18824055 [PubMed - as supplied by publisher]
Interaction of zinc with antidepressants in the tail suspension test.
Cunha MP, Machado DG, Bettio LE, Capra JC, Rodrigues AL Related Articles Interaction of zinc with antidepressants in the tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Sep 11; Authors: Cunha MP, Machado DG, Bettio LE, Capra JC, Rodrigues AL The antidepressant-like effect of zinc has been shown in several animal models of depression. In this study, zinc chloride (ZnCl(2)) was given alone or in combination with different classes of antidepressants by oral route (p.o.) to mice and the behavioral response in the tail suspension test (TST), a predictive test of depression, was investigated. ZnCl(2) at a dose of 10 and 30 mg/kg, p.o., reduced the immobility time in the TST, without affecting the locomotor activity in open-field test. The antidepressants fluoxetine, paroxetine, imipramine, desipramine and bupropion produced a significant reduction in the immobility time in TST at the doses of 10, 1, 1, 1 and 10 mg/kg, p.o., respectively. The combined treatment of sub-effective doses of ZnCl(2) (1 mg/kg) with sub-effective doses of fluoxetine (5 mg/kg), paroxetine (0.1 mg/kg), desipramine (0.1 mg/kg), imipramine (0.1 mg/kg) or bupropion (1 mg/kg) induced a significant reduction in the immobility time in the TST when compared with the groups treated with ZnCl(2) or with antidepressants alone. The treatment with sub-effective doses of ZnCl(2) and antidepressants alone or in combination did not affect the locomotion in open-field test, except that desipramine alone reduced the ambulation. The results first indicate that ZnCl(2) administered by p.o. route produces an antidepressant-like effect in the TST. Moreover, synergistic effects of zinc with antidepressants were shown in the TST, suggesting that an improvement in the response to the antidepressant therapy occurs when zinc is combined with different classes of antidepressants. PMID: 18824054 [PubMed - as supplied by publisher]

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