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Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A
Timothy J Craine1,2, Nicholas S Race1,3,4, Lindsay A Kutash1,3
1Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Journal of Neurotrauma
|August 18, 2022
Summary
Traumatic brain injury (TBI) impairs executive function. Milnacipran (MLN) treatment normalized cognitive flexibility deficits in rats after frontal lobe TBI, suggesting therapeutic potential for TBI recovery.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Traumatic brain injuries (TBIs) cause significant long-term cognitive and psychosocial deficits worldwide.
- Frontal lobe TBIs commonly impair executive functions, yet laboratory models often overlook these specific impairments.
- Assessing cognitive flexibility is crucial for understanding and treating TBI-related executive dysfunction.
Purpose of the Study:
- To implement a multi-modal approach for assessing frontal lobe function after TBI in rats.
- To evaluate the therapeutic potential of milnacipran (MLN), a serotonin-norepinephrine reuptake inhibitor, in mitigating TBI-induced cognitive deficits.
- To validate the sensitivity of attentional set-shifting tasks (AST) in detecting executive function impairments post-TBI.
Main Methods:
- Adult male rats underwent unilateral frontal lobe controlled cortical impact (CCI) or sham injury.
- Rats were treated with milnacipran (MLN) or vehicle (VEH) via osmotic minipumps.
- Cognitive flexibility was assessed using two distinct attentional set-shifting tasks (oAST and dAST) post-injury.
Main Results:
- Rats with TBI and vehicle treatment exhibited significant deficits in cognitive flexibility, indicated by increased trials and errors on both ASTs.
- Milnacipran treatment significantly normalized the performance deficits observed in TBI+VEH rats on both oAST and dAST.
- The dual AST approach proved sensitive and robust in detecting subtle executive function impairments following frontal lobe TBI.
Conclusions:
- The study demonstrates the utility of simultaneous operant and digging ASTs for evaluating executive function deficits after frontal lobe TBI in rats.
- Chronic administration of milnacipran shows promise in attenuating cognitive flexibility impairments post-TBI.
- These findings warrant further investigation into MLN as a potential therapeutic agent for TBI recovery.
