Effects of low doses of the novel dehydroepiandrosterone (DHEA) derivative BNN27 in rat models of anxiety

Abstract

Abstract Rationale Several lines of evidence indicate that the neurosteroid dehydroepiandrosterone (DHEA) is involved in anxiety. BNN27 is a new DHEA derivative lacking steroidogenic effects. The beneficial effects exerted by BNN27 in preclinical models of schizophrenia and memory disorders have been recently reported. Objectives The present study was designed to investigate the effects of this DHEA novel analog on anxiety-like behavior in rats. Methods To this end, the light/dark box, the open field, the contextual fear conditioning, and the excessive self-grooming induced by the serotonin 5-HT2c receptor agonist mCPP tests were utilized. Results Animals treated acutely with BNN27 (1, 3, and 6 mg/kg) dose dependently spent more time in the bright compartment of the light/dark box and in the central zone of the open field with respect to their vehicle-treated cohorts. Further, BNN27 reduced freezing behavior and weakened the mCPP-induced excessive self-grooming. Conclusions Our data indicate that BNN27 is a highly potent anxiolytic agent, as in all studied paradigms it showed anxiolytic-like effects in male rats.