Effects of Different SSRIs on nNOS mRNA Expression in the Hippocampus and Prefrontal Cortex of Chronically Stressed...

Depression severely affects the psychosocial functioning and quality of life of patients. Among first-line selective serotonin reuptake inhibitors (SSRIs), the incidence of neuropsychiatric side effects caused by paroxetine is 4-6 times higher than that caused by citalopram.

In this study, a depression model was established using Wistar rats to examine the effects of paroxetine and citalopram on neuronal nitric oxide synthase (nNOS) mRNA expression in the prefrontal cortex and hippocampus and to clarify the possible mechanisms of SSRI-induced neuropsychiatric side effects.

In the hippocampus, nNOS expression was significantly higher in the depression group than in the control group. However, in the prefrontal cortex, nNOS expression was significantly lower in the depression group than in the control group. Following the administration of postsynaptic density protein 95 (PSD-95)/nNOS inhibitor ZL006, nNOS levels decreased significantly in the paroxetine group but showed no significant change in the citalopram group.

The mechanisms regulating nNOS expression differed between the paroxetine and citalopram groups. Paroxetine-induced nNOS expression may be associated with PSD-95/nNOS.