Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

摘要: Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting state antidepressant resistance male Wistar rats using 21 days adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, effect ACTH on efficacy imipramine (10 mg kg(-1)) was investigated alongside its prefrontal cortex (PFC) mitochondrial function. Second, examined mood-regulatory actions chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) concomitant PFC Antidepressant-like responses were assessed open field test (OFT) forced swim (FST) for both conditions. pretreatment prevented imipramine-mediated improvement mobility during FST (P 0.05). Analyses function revealed that ACTH-treated animals had decreased capacity adenosine triphosphate production compared with controls. In contrast, following NAc DBS demonstrated greater relative to Interestingly, proportion (30%) exhibited heightened locomotor activity OFT exaggerated escape behaviors FST, together general hyperactivity their home-cage settings. More importantly, induction this mania-like phenotype accompanied by overcompensative increased respiration. Manifestation DBS-induced imipramine-resistant highlights potential use elucidating mechanisms dysregulation.