Finasteride administration potentiates the disruption of prepulse inhibition induced by forced swim stress.
Acute stress has been demonstrated to alter sensory gating processes, measured by the prepulse inhibition of the startle response (PPI). It is well known that brain and plasma levels of the neurosteroid allopregnanolone (ALLO) increase after acute environmental stress, fact that has been considered a homeostatic mechanism in restoring normal function following stress. Thus, it is of great interest to study the contribution of stress-altered plasma ALLO levels on PPI function. For this purpose, animals were injected with finasteride, an ALLO synthesis inhibitor, and submitted to swim stress before PPI testing. In order to obtain ALLO plasma levels, a separate set of animals that followed the same experimental procedure was used. We hypothesize that the blockade of ALLO production in response to stress can increase the stress-induced PPI disruption. In accordance with other authors, our results indicate that acute swim stress disrupted the normal PPI evolution (increase) related to the increase in prepulse intensities, and also decreased PPI at the highest prepulse intensity level (15 db above background). Finasteride potentiated the PPI decrease induced by swim stress in the intermediate prepulse intensity (10 db above background). As expected, plasma ALLO levels were increased in stressed animals and this increase was neutralized by prior finasteride administration. These results indicate that the neutralization of the physiological plasma ALLO levels increase after acute stress potentiates stress-induced PPI disruption. This data suggests that alterations in homeostatic ALLO synthesis mechanism may be linked to some neuropsychiatric disorders related to stress, such as anxiety/depression disorders.
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Edifici B, campus UAB, 08193 Bellaterra, Barcelona, Spain. Electronic address: marc.pallares@uab.es.
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Pallarès
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Edifici B, campus UAB, 08193 Bellaterra, Barcelona, Spain.
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Llidó
Present address: INMED, INSERM U901, Aix-Marseille Université, Parc Scientifique de Luminy, BP.13, 13273 Marseille cedex 9, France.
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Mòdol
Institut National de la Santé et de la Recherche Medicale (INSERM), Unité 862, Bordeaux, France.
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Vallée
Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, Edifici B, campus UAB, 08193 Bellaterra, Barcelona, Spain.
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Darbra
D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage*; D000818:Animals; D018120:Finasteride / Q000008:administration & dosage*; D008297:Male; D011280:Pregnanolone / Q000097:blood; D065808:Prepulse Inhibition / Q000187:drug effects*; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology*; D013550:Swimming
D058891:5-alpha Reductase Inhibitors; D018120:Finasteride; D011280:Pregnanolone
Acute swim stress; Allopregnanolone; Finasteride; Neurosteroids; Prepulse inhibition; Sensory gating