An aged-rat study linked amphetamine treatment with improved memory-task performance, restored stimulated norepinephrine release and changes in dendritic spines. These preclinical findings do not establish treatment efficacy or dementia prevention in older humans.
Scognamiglio and colleagues studied male Fischer 344 rats, comparing young animals with animals aged 18–22 months. Behavioral experiments used novel-object recognition and the Barnes maze, while tissue experiments examined neurotransmitter release from cortical and hippocampal preparations.
Acute studies used injected d-amphetamine; chronic studies administered it in drinking water. The tissue-release assay tracked radiolabeled norepinephrine after stimulation. These are neither clinical cognitive tests nor measurements of amphetamine in human blood.
Aged tissue showed reduced glutamate-stimulated norepinephrine release, with pharmacological evidence involving NMDA receptors. Amphetamine restored the release response. Behavioral improvements were reduced by propranolol, supporting a role for beta-adrenergic signaling.
Chronic treatment also accompanied changes in spine density and morphology. Such findings provide converging mechanistic evidence, but do not prove that the spine changes alone caused the measured memory improvement. Amphetamine affects more than one neurotransmitter system.
The study used one rat strain and male animals. Behavioral tasks depend on exploration, motivation and other processes in addition to memory, and animal aging does not reproduce every cause of human cognitive decline.
The results therefore justify further investigation rather than a clinical prescription or prevention claim. They do not show that amphetamine prevents dementia, repairs an individual human brain or is appropriate for every older adult. Nor can a tissue neurotransmitter result be converted into an individual concentration–impairment relationship.
Read our analysis of another example of separating measured and modeled rat outcomes.
Restoration of norepinephrine release, cognitive performance, and dendritic spines by amphetamine in aged rat brain. doi:10.1111/acel.14087.