Implication of Glutamatergic Mechanism for the Behavioral Changes Resulting from Early Maternal Separation during the Development in Juvenile Rats / 대한정신약물학회지

ABSTRACT

OBJECTIVE: Early maternal separation (EMS) during the development has been known to influence the alteration of behavior in adulthood. Nitric oxide (NO) may have been implicated to play a crucial role in the neurodevelopment as an intracellular and intercellular messenger. This study was designed to investigate the neurochemical mechanism of the behavioral changes resulting from EMS during the development in juvenile rats. METHODS: Experimental group consisted of subjects that were removed and weaned from the day on postnatal day 15. Control group were the litters that experienced no EMS until postnatal day 21. On postnatal day 15 and 36, the locomotor activity (LA) was measured. On postnatal day 36 the behavioral changes in the forced swimming test (FST) were also measured. Test drugs were intraperitoneally injected including MK-801 (0.5 mg/kg), N omega-nitro-L-arginine (L-NA, 20 mg/kg), paroxetine (20 mg/kg), and bupropion (150 mg/kg). RESULTS:EMS produced the decrease of LA significantly in juvenile rats (p<0.001). Both MK-801 and L-NA increased LA in experimental group (p<0.001) and control group (p<0.05). The degree of increase was higher in experimental group than in control group. However, both paroxetine and bupropion increased LA in experimental group (p<0.001, p<0.05), but not in control group. In the FST, immobility was significantly increased in experimental group compared with control group (p<0.001). The increases of immobility in experimental group were abolished after injecting MK-801, L-NA, paroxetine, and bupropion, respectively. CONCLUSION: These results indicate that EMS during the development can lead to behavioral abnormalities in juvenile rats. The underlying neurochemical mechanism of this behavioral changes may be, in part, related to the glutamatergic NMDA-NO pathway. This suggests that glutamatergic NMDA-NO pathway vulnerable to stress may predispose to depression.