Selank Reduces Dopamine Overactivity in Mice, Opioid System Implicated

The dopamine system plays a critical role in mood, motivation, and reward, but its hyperfunction is implicated in severe neurological and psychiatric conditions like schizophrenia and psychosis, often leading to anxiety. Current treatments, while effective, can have significant side effects due to direct dopamine receptor modulation. This study aimed to investigate the anxiolytic peptide Selank's mechanism of action on dopamine system overactivity and whether it involves the endogenous opioid system.

The study found that Selank significantly and dose-dependently reduced the behavioral manifestations of dopamine system hyperfunction in mice across all tested doses, from 0.01 to 10.0 mg/kg. This observed effect was quantitatively comparable to the reductions achieved by the atypical antipsychotic olanzapine at its near-therapeutic doses of 0.1 and 1.0 mg/kg. > Crucially, the beneficial effect of Selank on dopamine-induced behaviors was completely abolished when naloxone was co-administered at 10 mg/kg, indicating a strong dependence on the endogenous opioid system. However, radioreceptor assays revealed that Selank did not directly displace (3)H-spiperone from D2-dopamine receptors (with an EC50 greater than 100 microM) nor 3H-DADLE from delta- and mu-opioid receptors (with an EC50 greater than 40 microM), suggesting an indirect modulatory action rather than direct receptor binding.