| OBJECTIVE:To elucidate the effect of ondansetron(OND),a 5-HT3 receptor antagonist, on the morphine-induced conditioned place preference(CPP) in mice and its possible mechanism. METHODS: Established a morphine CPP model in mice and observed the effect of OND on the model; Nitric oxide synthase(NOS) activity and Nitric oxide(NO) output were assessed with spectrophotometric analysis, concentration of cyclic guanosine monophosphate(cGMP) was measured with radioimmunoassay; and the spatial learning and memory in CPP mice were tested by Morris water maze task. RESULTS: Morphine(MOR, 1-5 mg·kg-1,sc) appeared to be enough for mice to obtain a significant place preference. When mice were pretreated with OND(0.01-1mg· kg-1,sc)only once 30 min before the testing phase, the place preference induced by MOR was not affected. In contrast, OND(0.01-0.1mg· kg-1,ip)was administered at each injection of MOR during the conditioning phase, the place preference induced by MOR was antagonized remarkably,But with the higher dose(1 mg· kg-1,ip),the antagonism became variable, and OND when given alone also seemed to potentially produce CPP in mice at this dose.OND(0.01 mg· kg-1,ip) also can significantly inhibit their enhanced NOS activity and NO output in the limbic system of CPP mice, However, it can't inhibit their decreased cGMP concentration in the limbic system of CPP mice. Moreover, OND could attenuate the impairment of the spatial learning and memory in CPP mice at this dose. CONCLUSION: At certain doses, OND may antagonize the acquisition, but not the expression, of Mor-induced CPP, the mechanism may be related to the suppression of up-regulation of NOS and NO, but the role may be produced through the mechanisms other than those producing cGMP signal. The other mechanism may be related to the attenuation of spatial learning and memory in CPP mice. Which suggests that OND might be potentially useful in the treatment of opiate dependence. |
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