抄録
Nicotine (NC) has been reported to cause both sedative and anxiogenic effects, and participation of various brain receptors, including brain cannabinoid (CB) receptors, has been demonstrated. In the present study, the behavioral effects of repeated NC were examined in male ICR mice. Methods and Results: In the repeated subcutaneous NC (0.5 mg/kg, 4 days) administration group, unlike the acute single dose group, prolonged anxiety-related behavioral alterations were observed in the elevated plus-maze test, and sedative hypolocomotion was also caused at an earlier time point. Furthermore, NC caused stress-related depressive behavioral alterations in the forced swimming test, and these alterations were prolonged by repeated administration. Against the anxiety-related symptoms, the serotonin receptor antagonist WAY 100635 and the mixed agonist/antagonist virodhamine provided significant antagonistic effects. For the early sedative hypolocomotion, the non-CB1/non-CB2 brain CB receptor agonist O2093 had some antagonist activity. Furthermore, O2093 and virodhamine antagonized the stress-related depressive behavioral alterations in the forced swimming test. Discussion and Conclusion: These results demonstrated a prolongation of the NC-induced anxiety-related and stress-related behavioral alterations by repeated administration, which was accompanied by early sedative effects and may contribute to the persistent use of this drug. Furthermore, a characteristic participation of brain CB receptors in these prolonged behavioral effects was elucidated.
