抄録
Repeated nicotine (NC) use has been reported to induce prolonged stress-related depressive behavioral symptoms, accompanied by anxiety-related symptoms. In the present study, the mechanisms responsible for NC-induced stress-related depressive symptoms were examined in male ICR mice. Methods and Results: In the repeated subcutaneous NC administration (0.3 mg/kg, 4 days) group, like the repeated immobilization stress (IM) treatment (10 minutes, 4 days) group, prolonged stress-related depressive behavioral symptoms were observed in both the forced swimming (FS) and the tail suspension (TS) tests. However, in the FS test, depressed swimming behaviors were observed in the IM group even at the 1 day time point after the last treatment. Against these behavioral symptoms, the benzodiazepine partial inverse agonist Ro 15-4513 and the mixed opioid agonist-antagonist buprenorphine, administered intraperitoneally before each NC treatment, as well as the previously reported cannabinoid (CB) ligands virodhamine and O2093, provided significant antagonistic effects. On the other hand, the antidepressants amitriptyline, clomipramine and fluvoxamine provided significant antagonistic effects only in the TS test. Discussion and Conclusion: These results support the contribution of benzodiazepine and opioid neurons, as well as CB neurons, to repeated NC-induced stress-related depressive behavioral symptoms. NC-induced stress-related symptoms may be differentiated from other depressive symptoms based on the absence of antagonistic effects by some known antidepressants in the FS test.
