RATIONALE: Selective delta opioid receptor agonists have been shown to produce antidepressant-like behavioral effects and increase brain-derived neurotrophic factor (BDNF) mRNA expression when given acutely, but the chronic effects of delta agonists have been less well characterized. OBJECTIVE: The present study examined the effects of chronic exposure to the delta agonist (+)BW373U86 (BW) on antidepressant-like behavior in the forced swim test and on BDNF mRNA expression in comparison to chronic treatment with the antidepressants fluoxetine, desipramine, bupropion, and tranylcypromine. METHODS: Sprague-Dawley rats were treated chronic ally with one of the above treatments and were tested for antidepressant effects in the forced swim test, and assayed for BDNF mRNA expression by in situ hybridization. RESULTS: Acute administration of 10 mg/kg BW produced a significant antidepressant-like effect in the forced swim test, while chronic (8- or 21-day) BW administration did not produce a significant antidepressant-like effect. When 10 mg/kg BW was administered for 8 days, it produced a significant increase in BDNF mRNA expression in the frontal cortex, while having no effect on BDNF expression when given for 21 days. Chronic bupropion and desipramine significantly decreased BDNF expression in the dentate gyrus of the hippocampus, while fluoxetine had no effect in any brain region. Chronic tranylcypromine produced a significant increase in BDNF expression in the CA1 region of the hippocampus. CONCLUSIONS: Chronic exposure to BW produces tolerance to most effects, although at differential rates. In addition, increased BDNF mRNA expression does not appear to be a common effect of chronic administration of various antidepressants.