Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

Rationale: A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. However, the neurochemical rationale behind this strategy needs to be further clarified. Objectives: We examined the effect of chronic citalopram and subchronic lithium, alone or in combination, on (a) serum levels of citalopram and lithium, (b) animal behaviour and (c) hippocampal serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) levels. Furthermore, we examined the serum level of citalopram and hippocampal 5-HT following one acute citalopram injection. Methods: Microdialysis in the freely moving animals was used to determine hippocampal 5-HT and 5-HIAA. The animal behaviour was examined in the open field and forced swim test. Results: We found that chronic administration of citalopram (20 mg/kg/24 h s.c.) significantly increased the 5-HT baseline relative to vehicle-treated rats. Addition of subchronic lithium (60 mmol/kg chow pellet p.o.) to chronic citalopram therapy further elevated the 5-HT levels. Moreover, we found acute citalopram (5 mg/kg s.c.) to increase the 5-HT level. The immobility time in the FST and the locomotion in the OF were unaffected by any treatments. Conclusions: The present results support the assumption that increases in hippocampal 5-HT neurotransmission may be important in the augmentatory effect of lithium.