Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment

Autor: Timothy J, Craine, Nicholas S, Race, Lindsay A, Kutash, Anna L, Iouchmanov, Eleni H, Moschonas, Darik A, O'Neil, Carlson R, Sunleaf, Aarti, Patel, Nima, Patel, Katherine O, Grobengeiser, Ian P, Marshall, Taylor N, Magdelinic, Jeffrey P, Cheng, Corina O, Bondi
Rok vydání: 2023
Předmět:
Zdroj: Journal of Neurotrauma. 40:112-124
ISSN: 1557-9042
0897-7151
Popis: Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN). Two attentional set-shifting tasks (AST) evaluated cognitive flexibility via the rats' ability to locate food-based rewards by learning, unlearning, and relearning sequential rule sets with shifting salient cues. Adult male rats reached stable pre-injury operant AST (oAST) performance in 3-4 weeks, then were isoflurane-anesthetized, subjected to a unilateral frontal lobe controlled cortical impact (2.4 mm depth, 4 m/sec velocity) or Sham injury, and randomized to treatment conditions. Milnacipran (30 mg/kg/day) or vehicle (VEH; 10% ethanol in saline) was administered intraperitoneally via implanted osmotic minipumps (continuous infusions post-surgery, 60 μL/h). Rats had a 10-day recovery post-TBI/Sham before performing light/location-based oAST for 10 days and, subsequently, odor/media-based digging AST (dAST) on the last test day (26-27 days post-injury) before sacrifice. Both AST tests revealed significant deficits in TBI+VEH rats, seen as elevated total trials and errors (
Databáze: OpenAIRE
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