Neurosteroid pregnenolone sulfate, alone, and as augmentation of lurasidone or tandospirone, rescues phencyclidine-induced deficits in cognitive function and social interaction

Behavioural Brain Research
Lakshmi RajagopalHerbert Y Meltzer

Abstract

Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients. We tested whether PregS, by itself, and in combination with Lur or Tan could rescue persistent deficits produced by subchronic treatment with the NMDAR antagonist, phencyclidine (PCP)-in episodic memory, executive functioning, and social behavior, using novel object recognition (NOR), operant reversal learning (ORL), and social interaction (SI) tasks, in male C57BL/6 J mice. PregS (10, but not 3 mg/kg) significantly rescued subchronic PCP-induced NOR and SI deficits. Co-administration of sub-effective doses (SEDs) of PregS (3 mg/kg) + Lur (0.1 mg/kg) or Tan (0.03 mg/kg) rescued scPCP-induced NOR and SI deficits. Further, PregS...Continue Reading

Citations

Apr 26, 2020·Journal of Clinical Psychopharmacology·Herbert Y MeltzerMyung A Lee
Jul 28, 2019·Molecular Genetics & Genomic Medicine·Eva Albertsen MaltHilde Loge Nilsen
Aug 11, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lakshmi RajagopalHerbert Y Meltzer
Dec 12, 2020·Scientific Reports·Natalja KurbatovaSimon Lovestone
May 7, 2020·Pharmacology, Biochemistry, and Behavior·Solenn PercelayMichel Boulouard

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