Effects of Age and Atomoxetine on Olfactory Perception and Learning and Underlying Plasticity Mechanisms in Rats
Bibliographic record
Abstract
The locus coeruleus (LC) plays a vital role in cognitive function through norepinephrine release. Impaired LC neuronal health and function is linked to cognitive decline during ageing and Alzheimer's disease. This study investigates age-related alterations in olfactory detection and discrimination learning, along with its reversal, in Long-Evans rats, and examines the effects of atomoxetine (ATM), a norepinephrine uptake inhibitor, on these processes. Adult (6-9 months) and aged (22-24 months) Long-Evans rats underwent odour detection threshold experiments with saline and two doses of ATM (0.3 and 1 mg/kg). Reward-based odour discrimination learning included simple, difficult and reversal learning tasks. LC neuron density, dopamine beta-hydroxylase and norepinephrine transporter expression in the piriform cortex (PC) and orbitofrontal cortex were measured. Reversal learning and olfactory threat extinction were used to measure behavioural flexibility. Immunohistochemistry and western blotting were used to analyse phosphorylated cAMP response element binding protein (pCREB) and cFos expression and ex vivo electrophysiology assessed long-term depression (LTD) in the PC. Whereas adult and aged cohorts showed similar odour detection and discrimination learning, fewer aged rats acquired reversal learning successfully. ATM improved reward-based odour discrimination in adults but hindered learning reversal. A delayed CREB phosphorylation in the posterior PC associated with atomoxetine administration possibly underlies learning enhancement. ATM resulted in less freezing behaviour in a threat conditioning and extinction paradigm at moderate, but not at higher doses. ATM administration ex vivo prevented PC LTD. These findings highlight the intricate effects of atomoxetine, influenced by target structures, and suggest potential interactions with other neurotransmitters. Our results contribute to understanding the impact of ageing and norepinephrine enhancers on cognitive processes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".