Combined chronic treatment with citalopram and lithium does not modify the regional neurochemistry of nitric oxide in rat brain.

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. Also inhibitors of nitric oxide synthase (NOS) have been used as an augmentation strategy, while inhibitors of NOS exhibit antidepressant-like properties in various animal models. Therefore, we hypothesized that modulation of NOS may be involved in the long-term effects of antidepressants and lithium, and studied the influence of acute and chronic administration of citalopram, alone or in combination with lithium, on NOS activity in hippocampus, cerebellum, and frontal cortex, by determination of L-citrulline being formed. We found that administration of acute or chronic citalopram (5 mg/kg and 20 mg/kg/24h, respectively) alone or in combination with subchronic lithium (60 mmol/kg chow pellet) did not influence the activity of NOS ex vivo in all regions compared to control. In contrast, high doses of lithium caused a significant decrease in NOS activity in vitro. We conclude that basal conditions are unsuitable for the study of antidepressant effects on NOS, and that the neurochemistry of nitric oxide remains unaltered following chronic citalopram or subchronic lithium under normal physiological conditions.

Nitric oxide modulates lithium-induced conditioned taste aversion.

Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.