Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress
|dc.identifier.citation||Frau, Roberto et al. “Targeting Neurosteroid Synthesis as a Therapy for Schizophrenia-Related Alterations Induced by Early Psychosocial Stress.” Schizophrenia research 168.3 (2015): 640–648.||en_US|
|dc.description.abstract||BackgroundCogent evidence has shown that schizophrenia vulnerability is enhanced by psychosocial stress in adolescence, yet the underpinnings of this phenomenon remain elusive. One of the animal models that best capture the relationship between juvenile stress and schizophrenia is isolation rearing (IR). This manipulation, which consists in subjecting rats to social isolation from weaning through adulthood, results in neurobehavioral alterations akin to those observed in schizophrenia patients. In particular, IR-subjected rats display a marked reduction of the prepulse inhibition (PPI) of the startle reflex, which are posited to reflect imbalances in dopamine neurotransmission in the nucleus accumbens (NAcc). We recently documented that the key neurosteroidogenic enzyme 5α-reductase (5αR) plays an important role in the dopaminergic regulation of PPI; given that IR leads to a marked down-regulation of this enzyme in the NAcc, the present study was designed to further elucidate the functional role of 5αR in the regulation of PPI of IR-subjected rats.MethodsWe studied the impact of the prototypical 5αR inhibitor finasteride (FIN) on the PPI deficits and NAcc steroid profile of IR-subjected male rats, in comparison with socially reared (SR) controls.ResultsFIN (25–100 mg/kg, i.p.) dose-dependently countered IR-induced PPI reduction, without affecting gating integrity in SR rats. The NAcc and striatum of IR-subjected rats displayed several changes in neuroactive steroid profile, including a reduction in pregnenolone in both SR and IR-subjected groups, as well as a decrease in allopregnanolone content in the latter group; both effects were significantly opposed by FIN.ConclusionsThese results show that 5αR inhibition counters the PPI deficits induced by IR, possibly through limbic changes in pregnenolone and/or allopregnanolone concentrations.||en_US|
|dc.rights||This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.||en_US|
|dc.title||Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress||en_US|
|kusw.kudepartment||Bureau of Child Research||en_US|
|kusw.oanotes||Per SHERPA/RoMEO 4/24/2017: Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions: Authors pre-print on any website, including arXiv and RePEC Author's post-print on author's personal website immediately Author's post-print on open access repository after an embargo period of between 12 months and 48 months Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months Author's post-print may be used to update arXiv and RepEC Publisher's version/PDF cannot be used Must link to publisher version with DOI Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License||en_US|
|kusw.oaversion||Scholarly/refereed, author accepted manuscript||en_US|
|kusw.oapolicy||This item meets KU Open Access policy criteria.||en_US|
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