Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioral models in rodents.
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 delta-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 delta-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 delta-opioid receptors may play an important role in the regulation of emotional responses. Furthermore, it is possible that delta-opioid-receptor agonists might be novel and potent antidepressants that also have anxiolytic-like effects.
Department of Pathophysiology & Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan.
Akiyoshi
A
Saitoh
Yuji
Y
Kimura
Tomohiko
T
Suzuki
Koji
K
Kawai
Hiroshi
H
Nagase
Junzo
J
Kamei
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D013315:Stress, Psychological; D013550:Swimming
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide