8-OH-DPAT(Egis Gyógyszergyár Zrt.)

Neural signals necessary for gaze holding are produced in the excitatory networks of oculomotor neural integrators including the prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC). Our previous studies have shown that the activation of the networks can be evaluated by sustained excitatory postsynaptic current (EPSC) responses in vitro, in which a higher EPSC frequency after burst stimulation (100 Hz, 20 trains) than the frequency before the stimulation lasts for >1 s. Both the PHN and the INC receive serotonergic inputs mainly from the dorsal raphe nucleus, and serotonin (5-HT) induces depolarizing responses via 5-HT 2 or 5-HT 3 receptors and hyperpolarizing responses via 5-HT 1A receptors in PHN and INC neurons. However, how 5-HT affects sustained EPSC responses remains unknown. In this study, we investigated the effects of 5-HT on sustained EPSC responses using whole-cell recordings in brainstem slices obtained from rats of either sex. Compared with the control treatment, bath application of 10 μM 5-HT significantly reduced the duration and frequency of the EPSC responses in the PHN and the INC. The application of 8-OH-DPAT, an agonist of the 5-HT 1A receptor, suppressed sustained EPSC responses, but agonists of the 5-HT 2 and 5-HT 3 receptors had no effect on the responses, indicating that 5-HT has a suppressive effect on sustained EPSC responses via 5-HT 1A receptors. These results suggest that neurons that express 5-HT 1A receptors participate in excitatory networks and that the suppressive effect of 5-HT can facilitate exploratory behavior through eye movements rather than gaze holding.

Anxiety is a normal emotion representing a reaction to potential danger, whereas fear can be defined as a reaction to real, explicit danger. Anxiety-like behavior in animal models has been associated with differences in the serotonergic system.

To understand the roles of the 5-HT1A receptor in zebrafish anxiety-like behavior and sociality.

Adult zebrafish were treated with 8-OH-DPAT and subjected to the phototaxis (light-dark preference) assay, the novel tank test (NTT), or the social preference test. Separate cohorts were treated with increasing doses of 8-OH-DPAT, while 5-HT1A receptors were blocked with a silent dose of WAY 100635.

8-OH-DPAT (0.3 mg/kg) decreased anxiety-like behavior in the NTT, but increased it in the phototaxis (light-dark preference) assay, both considered assays for anxiety-like behavior for this species. The same dose decreased social approach in both the social investigation and social novelty phases of the social preference test. Blocking the 5-HT1A receptor with WAY 100635 (0.01 mg/kg) shifted the dose–response curve (0.03–3 mg/kg) for the NTT rightward.

These effects suggest a participation of the 5-HT1A heteroreceptors in zebrafish anxiety and social preference, modulating anxiety in a test-dependent way and decreasing sociality. Thus, the study of this receptor is important for a better understanding of anxiety-like behavior in zebrafish and its relationship with similar phenomena in vertebrates.