Protective Effects of Amantadine Against Propofol-Associated Spatial Memory Impairment in Aged Mice

Aging is associated with progressive alterations in synaptic plasticity, NMDA receptor function, and neurotransmitter signaling that render the aging brain disproportionately vulnerable to anesthetic-associated cognitive disturbances. Propofol has been associated with hippocampus-dependent memory impairment in aged experimental models, yet pharmacological strategies to mitigate this vulnerability remain insufficiently explored.

Twenty-eight aged BALB/C mice were randomly assigned to four groups: control, propofol (75 mg/kg), amantadine (20 mg/kg), and propofol+amantadine (n = 7 each). Anesthetic induction and recovery were assessed using loss and return of the righting reflex. Locomotor activity and nociceptive responses were evaluated using the open-field and hot plate tests. Spatial memory was assessed using the Morris water maze at three time points following drug administration.

Time to loss of righting reflex did not differ between propofol-treated groups, whereas recovery from anesthesia occurred significantly earlier in animals receiving amantadine with propofol. Locomotor activity was comparable among groups. Propofol exposure was associated with significantly impaired spatial memory, while animals receiving amantadine with propofol demonstrated markedly better performance across all assessment time points.

Amantadine may mitigate anesthetic-associated spatial memory impairment and facilitate anesthetic recovery in the aging brain, supporting further investigation of neuromodulatory strategies targeting cognitive vulnerability in aged populations.