Objective To observe the effect of electroacupuncture(EA) intervention at different time in a day on the expression of tyrosine hydroxylase(TH) and c-fos in the Nucleus Accumbens(NAc) so as to explore its mechanism underlying improvement of ketamine addiction.Methods A total of 56 Sprague-Dawley rats were randomized into normal control

normal saline(2 mL/kg)

model and EA groups.The EA group was subdivided into Zi-Shi(23:00)

Mao-Shi(05:00)

Wu-Shi(11:00) and You-Shi(17:00) subgroups.Ketamine addiction model was established by intraperitoneal administration of ketamine(100 mg/kg)

once a day for 7 days.EA(2 Hz

3 V) was applied to unilateral "Zusanli"(ST 36) and "Sanyinjiao"(SP 6) for 30 min

once daily for 7 days.The expression of TH and c-fos in the NAc was detected by immunohistochemistry.Results Compared with the normal control group and normal saline group

the numbers of TH and c-fos immunoreaction(IR)-positive neurons in NAc in the model group were upregulated significantly(P<0.01).Compared with the model group

the expression levels of both TH and c-fos IR-positive neurons were down-regulated significantly in the Wu-Shi(11:00) and You-Shi(17:00) subgroups(P<0.01)

rather than in the Zi-Shi and Mao-Shi subgroups(P>0.05).Conculsion EA of "Zusanli"(ST 36) and "Sanyinjiao"(SP 6) at 11:00 and 17:00 of the daytime can down-regulate ketamine addiction induced increase of expression of TH and c-fos in the NAc in ketamine addiction rats

which may contribute to its effect in relieving ketamine addiction symptoms in clinic.