The cross-talk between dopaminergic and nitric oxide systems in the medial septal nucleus, and their distinct effects on anxiety-like behaviors in male rats

Anxiety disorders, which have a noticeable global prevalence and may be caused by many factors, include a spectrum of disorders that share features of excessive fear- and anxiety-related behavioral disturbances. Different brain areas and neurotransmitter systems have been under investigation for anxiety-related disorders. In this study, we investigated the possible interaction between the dopaminergic and nitric oxide (NO) neurotransmitter systems in the medial septal nucleus and their roles in anxiety-like behaviors using elevated plus-maze (EPM) test in male rats. Our results showed that: (i) both D1-and D2-like receptor agonists, SKF-38393 and quinpirole, augmented anxiety-like behaviors at their two highest applied doses in the EPM test; (ii) both D1-and D2-like receptor antagonists, SCH- 23390 and sulpiride, reduced anxiety-like behaviors at their two highest applied doses in the EPM test; (iii) L-Arginine, a NO precursor, increased anxiety-like behaviors, but L-NAME, a non-specific nitric oxide synthase (NOS) inhibitor, reduced them in the EPM test; (iv) L-NAME could not reverse the anxiety-like parameters produced by SKF-38393, but it significantly reduced the anxiety-like behaviors induced by quinpirole; (v) Neither SCH- 23390 nor sulpiride changed anxiety-related behaviors induced by L-Arginine. It can be concluded that both dopaminergic and nitric oxide systems in the medial septal nucleus are involved in modulating anxiety-like behaviors. While NO has an involvement in the exerted effects by the D2-like agonist, such effects were not observed at the applied range of the doses for D1-and D2-like antagonists.