Serotonin₆ Receptors in the Prelimbic Cortex are Involved in the Regulation of Anxiety-Like Behaviors in the Rat 6-Hydroxydopamine Parkinson’s Disease Model.

The role of serotonin₆ (5-HT₆) receptors in the regulation of anxiety is poorly understood, particularly in Parkinson’s disease-related anxiety. Here we examined whether 5-HT₆ receptors in the prelimbic cortex (PrL) involve in the regulation of anxiety-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced anxiogenic responses as measured by the open-field and elevated-plus maze tests compared to sham-operated rats. Intra-PrL injection of 5-HT₆ receptor agonist WAY208466 (0.5, 3 and 6 μg/ rat) decreased the percentage of time spent in the center area of the open field and percentages of open arm entries and open arm time in sham-operated rats, indicating the induction of anxiogenic responses, and injection of 5-HT₆ receptor antagonist SB258585 (1, 2, and 4 μg/rat) showed anxiolytic effects. Interestingly, WAY208466, at the same doses, increased the percentage of time spent in the center area of the open-field and percentages of open arm entries and open arm time in the lesioned rats, indicating the induction of anxiolytic effects, and SB258585, at the same doses, produced anxiogenic responses. Collectively, our findings indicate that 5-HT₆ receptors in the PrL are involved in the regulation of anxiety-like behaviors, which may attribute to changes in dopamine and noradrenaline levels in the limbic and limbic-related brain regions after activation and blockade of PrL 5-HT₆ receptors.