PMID- 14647482 OWN - NLM STAT- MEDLINE DCOM- 20040517 LR - 20161124 IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 29 IP - 4 DP - 2004 Apr TI - The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in rats. PG - 649-59 AB - delta-Opioid receptor agonists have antidepressant-like effects in behavioral models of depression. Chronic administration of classical antidepressants upregulates mRNA expression of brain-derived neurotrophic factor (BDNF) and its high-affinity tyrosine kinase receptor, TrkB in the frontal cortex and hippocampus of rats. Increases in BDNF and TrkB levels are thought to be important for the therapeutic effects of these drugs. Therefore, we examined the ability of the delta-opioid receptor agonist (+)BW373U86 to regulate BDNF and TrkB mRNA expression in frontal cortex, hippocampus, as well as, basolateral amygdala, endopiriform nucleus, and primary olfactory cortex. At 3 h after a single administration of (+)BW373U86 animals were killed and BDNF and TrkB mRNA levels were examined by in situ hybridization. BDNF mRNA levels produced by (+)BW373U86 were compared to acute administration of the antidepressants desipramine and bupropion. A behaviorally antidepressant dose of 10 mg/kg (+)BW373U86 increased BDNF mRNA expression in all regions examined; a smaller dose of (+)BW373U86 (1 mg/kg) significantly increased BDNF mRNA expression only in frontal cortex. The delta-opioid receptor antagonist naltrindole blocked (+)BW373U86-mediated increases in BDNF mRNA expression. In addition, tolerance developed to increased BDNF mRNA expression with repeated injection, except in frontal cortex. Midazolam was administered to some animals to prevent the convulsions produced by (+)BW373U86, but midazolam did not block delta-opioid receptor-mediated increases in BDNF mRNA expression in frontal cortex, hippocampus, or amygdala. Unlike desipramine and bupropion, (+)BW373U86 upregulated BDNF mRNA expression acutely (within 3 h after a single administration). These data support the concept that delta-opioid receptor agonists may have antidepressant potential, and could be good targets for the development of faster-acting antidepressants. FAU - Torregrossa, Mary M AU - Torregrossa MM AD - Neuroscience Doctoral Program, University of Michigan, Ann Arbor, MI, USA. FAU - Isgor, Ceylan AU - Isgor C FAU - Folk, John E AU - Folk JE FAU - Rice, Kenner C AU - Rice KC FAU - Watson, Stanley J AU - Watson SJ FAU - Woods, James H AU - Woods JH LA - eng GR - DA00254/DA/NIDA NIH HHS/United States GR - DA07281/DA/NIDA NIH HHS/United States GR - DA13386/DA/NIDA NIH HHS/United States GR - MH42251/MH/NIMH NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Anti-Anxiety Agents) RN - 0 (Antidepressive Agents) RN - 0 (Benzamides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Narcotic Antagonists) RN - 0 (Piperazines) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Opioid, delta) RN - 01ZG3TPX31 (Bupropion) RN - 150428-54-9 (BW 373U86) RN - 5S6W795CQM (Naltrexone) RN - EC 2.7.10.1 (Receptor, trkB) RN - G167Z38QA4 (naltrindole) RN - R60L0SM5BC (Midazolam) RN - TG537D343B (Desipramine) SB - IM MH - Analysis of Variance MH - Animals MH - Anti-Anxiety Agents/pharmacology MH - Antidepressive Agents/pharmacology MH - Behavior, Animal/drug effects MH - Benzamides/*pharmacology MH - Brain/anatomy & histology/drug effects MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Bupropion/pharmacology MH - Desipramine/pharmacology MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Interactions MH - Drug Tolerance MH - Gene Expression Regulation/*drug effects MH - Immobilization MH - In Situ Hybridization/methods MH - Male MH - Midazolam/pharmacology MH - Naltrexone/*analogs & derivatives/pharmacology MH - Narcotic Antagonists/pharmacology MH - Piperazines/*pharmacology MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/genetics/metabolism MH - Receptors, Opioid, delta/*agonists MH - Swimming MH - Time Factors MH - Up-Regulation EDAT- 2003/12/03 05:00 MHDA- 2004/05/18 05:00 CRDT- 2003/12/03 05:00 PHST- 2003/12/03 05:00 [pubmed] PHST- 2004/05/18 05:00 [medline] PHST- 2003/12/03 05:00 [entrez] AID - 1300345 [pii] AID - 10.1038/sj.npp.1300345 [doi] PST - ppublish SO - Neuropsychopharmacology. 2004 Apr;29(4):649-59. doi: 10.1038/sj.npp.1300345.