To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated (i.p.) with saline or morphine 10 mg/kg twice daily for 3 d and then drug...To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated (i.p.) with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine (10 mg/kg) was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan (5-HTP), a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment (induction), during the morphine treatment suspension (transfer) or prior to the challenge dose of morphine (expression) and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.展开更多
基金National Natural Science Foundation of China (Grant No. 30570653)National Basic Research Program of China (Grant No. 2003CB515400)985 Program of China Ministry of Education
文摘To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated (i.p.) with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine (10 mg/kg) was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan (5-HTP), a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment (induction), during the morphine treatment suspension (transfer) or prior to the challenge dose of morphine (expression) and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.