 | Increases in BDNF and TrkB levels are thought to be important for the therapeutic effects of these drugs. The delta-opioid receptor antagonist naltrindole blocked ( )BW373U86-mediated increases in BDNF mRNA expression. 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 embittered BDNF mRNA expression only in frontal cortex. BDNF mRNA levels produced by ( )BW373U86 were compared to acute administration of the antidepressants antidepressants desipramine and Bupropion ( Wellbutrin SR ). At 3 h after a single administration of ( )BW373U86 animals were killed and BDNF and TrkB mRNA levels were examined by in situ hybridization. The delta-opioid receptor agonist ( wellbutrin )BW373U86 regulates BDNF mRNA expression in rats.delta-Opioid receptor agonists have antidepressant-like effects in behavioral models of depression. 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. 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.
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.. Unlike desipramine and Bupropion ( Wellbutrin SR ), ( )BW373U86 upregulated BDNF mRNA expression acutely (within 3 h after a single administration). In addition, tolerance developed to increased BDNF mRNA expression with perpetual injection, except in bupropion sr frontal cortex. 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.
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| Last access: | Sunday, 15 March 2009, 11:45 AM (330 days 11 hours) |
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