In the present study, we investigated the antidepressant- and anxiolytic-like effects of (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80), a non-peptidic selective δ-opioid receptor agonist, in various animal models in rodents. SNC80 significantly reduced the duration of immobility in the forced swimming test. Furthermore, in the elevated plus-maze test, SNC80 dose-dependently and significantly increased the time spent in the open arms of the plus-maze. These effects were completely antagonized by a selective δ-opioid-receptor antagonist, naltrindole. In the conditioned fear stress test, which examines psychological stress-induced motor suppression, desipramine did not produce any significant effect on the conditioned suppression of locomotor activity. However, SNC80 completely attenuated the conditioned suppression of locomotor activity in the conditioned fear stress test. In conclusion, our results suggest that δ-opioid receptors may play an important role in the regulation of emotional responses. Furthermore, it is possible that δ-opioid-receptor agonists might be novel and potent antidepressants that also have anxiolytic-like effects.
The Japanese Pharmacological Society 2004