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Biochem Biophys Res Commun. 2000 Nov 11;278(1):150-7.
Identification of a novel gene with RING-H2 finger motif induced after chronic antidepressant treatment in rat brain.
Yamada M, Yamada M, Yamazaki S, Takahashi K, Nishioka G, Kudo K, Ozawa H, Yamada S, Kiuchi Y, Kamijima K, Higuchi T, Momose K.
Department of Psychiatry, School of Medicine, Showa University, Tokyo 142-8666, Japan.
Previously, we have identified 200 cDNA fragments as antidepressant related genes/ESTs. In this study, using these cDNAs, we developed our original cDNA microarray for rapid secondary screening of candidate genes as the novel therapeutic targets. With this microarray, we found that the expression of a novel gene, ADRG34, was significantly increased in rat hippocampus which had been chronically treated with a selective serotonin reuptake inhibitor antidepressant, sertraline. RT-PCR analysis also demonstrated the induction of ADRG34 at mRNA levels in rat hippocampus and the frontal cortex. This cDNA encoded 685 amino acid residues containing a RING-H2 finger motif at the carboxy-terminal. Sequence analysis of ADRG34 with the EMBL/GenBank database showed significant homology to mouse and human kf-1 gene. Our data suggest that ADRG34, a possible rat homologue of kf-1, may be one of the common functional molecules induced after chronic antidepressant treatment. Copyright 2000 Academic Press.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11071867&dopt=Abstract
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Eur J Pharmacol. 2000 Nov 24;408(3):257-63.
Do antidepressants affect motivation in conditioned place preference?
Subhan F, Deslandes PN, Pache DM, Sewell RD.
Neuropharmacology Drug Action Group, Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cathays Park, CF10 3XF, Cardiff, UK.
The positive motivational effects of a range of antidepressants/neurotransmitter reuptake inhibitor compounds were studied using conditioned place preference. These agents included amitriptyline (2.5-10 mg/kg), venlafaxine (5 and 10 mg/kg), sibutramine (5 and 10 mg/kg), fluoxetine (2.5-10 mg/kg), paroxetine (5-15 mg/kg) and sertraline (2.5-10 mg/kg). Male Wistar rats were place conditioned in a three-compartment box to vehicle or drug alternately for 8 days using a 30-min pretreatment time. Control animals received vehicle only. Cocaine (5 mg/kg) was used as a positive control for the procedure. Significant place preference (P<0.05) was observed with paroxetine (15 mg/kg), fluoxetine (5 and 10 mg/kg), sertraline (2.5-10 mg/kg) and cocaine. Venlafaxine and sibutramine, serotonin/noradrenaline reuptake inhibitors, produced no place conditioning, while the highest dose of the tricyclic antidepressant, amitriptyline (10 mg/kg), produced signs of place aversion. The role of serotonin in reward pathways and differences in serotonin, noradrenaline and dopamine reuptake-inhibiting properties of these compounds may explain why only the serotonin-selective reuptake inhibitors produced place preference in this study.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11090642&dopt=Abstract
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ext.jussieu.fr
OBJECTIVE: To establish the therapeutic effect profile of sertraline in major depression. It was hypothesized that the antidepressant effect of sertraline showed three phases: Phase 1 where improvements in anxiety are most pronounced; Phase 2 where the greatest improvements are in depressive symptoms; and Phase 3 where the symptoms of anhedonia show the most improvement. To test this hypothesis, an 8-week, open-label study was conducted. METHODS: Patients with a major depressive episode (DSM-IV) and a score > or = 24 on the 17-item HAM-D were enrolled and treated with sertraline 50-150 mg/day. The three symptomatic clusters, anxiety, depression and hedonia, were defined a priori using the Inventory of Depressive Symptomatology-Clinician rated (IDS-C). Periods of interest were: Days 0-7 for anxiety, Days 7-21 for depression and Days 21-56 for anhedonia. Raters were blinded as to the constitution of the clusters and periods. RESULTS: 140 patients were recruited. Improvement in the anxiety cluster of the IDS-C was greatest during Days 0-7, whereas over Days 7-21 most improvement was observed in the depression cluster and the greatest improvement in the hedonic cluster occurred during Days 21-56. CONCLUSION: These preliminary results are consistent with the hypothesis that the therapeutic effects of sertraline occur in a sequential manner. The symptoms of anxiety improved first, followed by depression and then anhedonia.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11123488&dopt=Abstract
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