Effects of ketamine plus fluoxetine on nNOS and CAPON expression in the prefrontal lobe of mentally depressed rats
10.3969/j.issn.1001-1978.2015.04.010
- VernacularTitle:氯胺酮联合氟西汀对抑郁大鼠前额叶nNOS及其配体CAPON表达的影响
- Author:
Yiwei SHEN
;
Feng LYU
;
Ping LI
;
Jie LUO
;
Fei XIE
;
Su MIN
- Publication Type:Journal Article
- Keywords:
ketamine;
fluoxetine;
depression;
pre-frontal lobe;
nitirc oxide synthase;
CAPON
- From:
Chinese Pharmacological Bulletin
2015;(4):487-492
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of ketamine plus fluoxetine on depressed behavior and the expres-sion of neuronal nitric oxide synthase (nNOS)and CA-PON in prefrontal lobe of mentally depressed rats at different time points,so as to study the possible mecha-nism of ketamine plus fluoxetine inducing antidepres-sant behavior.Methods Healthy adult male Sprague-Dawley rats,aged 2.5 ~3 months,weighing 220 ~270 g,were induced as the rodent model of depression by chronic unpredictable mild stress (CUMS).After the models of depression were established,96 of CUMS modeling successfully depressed rats were selected. Then they were randomly divided into four groups (n =24 each):the depressed group (group D,untreated group),ketamine group (group K,treated with intrap-eritoneal injection of ketamine 1 0 mg·kg -1 once a day for 3 days or 7 days),fluoxetine group (group F,trea-ted with gavage of fluoxetine 1 .8 mg·kg -1 once a day for 3 days or 7 days),or ketamine plus fluoxetine group (group KF,treated with intraperitoneal injection of ketamine 1 0 mg·kg -1 plus gavage of fluoxetine 1 .8 mg·kg -1 once a day for 3 days or 7 days).Open field test and sucrose preference test were performed 1 day before depression model was established,and 1 day before and after treatment.The rats were sacrificed 1 day after the last test for determination of the expres-sion of nNOS and CAPON protein (using immuno-his-tochemisity)and mRNA (by RT-PCR)in the prefron-tal lobe.Results After the models of depression were established,the total distance,rearing number and the sucrose preference percentage (SPP)were decreased significantly compared with those before (P <0.05). There was no significant difference among all groups in the total distance,rearing number and the SPP before treatment (P >0.05 ).Compared with groups D and F,the total distance was prolonged,the number of rea-ring and SPP were significantly increased,the expres-sion of nNOS protein and mRNA was down-regulated and the expression of CAPON protein and mRNA was up-regulated in groups K and KF,with 3 days’treat-ment (P <0.05).Compared with group D,the total distance was prolonged,the number of rearing and SPP were significantly increased,the expression of nNOS protein and mRNA was down-regulated and the expres-sion of CAPON protein and mRNA was up-regulated in groups K,F and KF with 7 days’treatment (P <0.05).Compared with group F,the total distance was prolonged,the number of rearing and SPP were signifi-cantly increased,the expression of nNOS protein and mRNA was down-regulated and the expression of CA-PON protein and mRNA was up-regulated in group KF with 7 days’treatment (P <0.05).Conclusion Co-administration of antidepressant fluoxetine with ket-amine may induce a more pronounced antidepressant activity than treatment with each antidepressant alone and it can shorten the time to improve the depressive state through promoting the expression of CAPON and inhibiting nNOS activity in the prefrontal lobe of men-tally depressed rats.
