The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts cognitive deficits induced by the D1/D2 dopaminergic receptor agonist apomorphine in rats

• Published in: Psychopharmacology 2021, Vol.238 (1), p.227-237
• Main Authors: Pitsikas, Nikolaos, Zoupa, Elli, Gravanis, Achille
• Format: Article
• Language: English
• Subjects: Agonists; Animals; Apomorphine; Apomorphine - pharmacology; Biomedical and Life Sciences; Biomedicine; Care and treatment; Cognition - drug effects; Cognitive ability; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - prevention & control; Cognitive Dysfunction - psychology; Complications and side effects; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Dopamine; Dopamine - metabolism; Dopamine Agonists - pharmacology; Dopamine D1 receptors; Dopamine D2 receptors; Dopaminergic mechanisms; Dosage and administration; Innovations; Locomotion - drug effects; Locomotor activity; Male; Medical examination; Memory; Memory - drug effects; Memory Disorders - metabolism; Memory Disorders - prevention & control; Memory Disorders - psychology; Mental disorders; Neurosciences; Neurosteroids; Neurotrophic functions; Original Investigation; Patient outcomes; Pattern recognition; Pharmacology/Toxicology; Psychiatry; Rats; Rats, Wistar; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D2 - agonists; Recognition, Psychology - drug effects; Schizophrenia; Schizophrenia - metabolism; Spatial memory; Steroid hormones
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-020-05672-z

Rationale Schizophrenia is a devastating mental disease that affects nearly 1% of the population worldwide. It is well documented that the dopaminergic (DAergic) system is compromised in schizophrenia. It is of note that the mixed dopamine (DA) D 1 /D 2 receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Neuroactive steroids, comprising dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS), were shown to affect brain DAergic system and to be involved in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. It has recently been reported that BNN27 counteracted schizophrenia-like behavioural deficits produced by glutamate hypofunction in rats. Objectives The aim of the present study was to investigate the ability of BNN27 to attenuate non-spatial, spatial recognition and discrete memory deficits induced by apomorphine in rats. Methods To this end, the object recognition task (ORT), the object location task (OLT) and the step-through passive avoidance test (STPAT) were used. Results BNN27 (3 and 6 mg/kg, i.p.) attenuated apomorphine (0.5 mg/kg, i.p.)-induced non-spatial, spatial recognition and discrete memory deficits. Interestingly, the effects of compounds on memory cannot be ascribed to changes in locomotor activity. Conclusions Our findings suggest that BNN27 is effective to DA dysfunction caused by apomorphine, attenuating cognitive impairments induced by this D1/D2 receptor agonist in rats. Additionally, our findings illustrate a functional interaction between BNN27 and the DAergic system that may be of relevance for schizophrenia-like behavioural symptoms.