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A neurotoxic regimen of methamphetamine impairs novelty recognition as measured by a social odor-based task
Steven J O'Dell1, Leila M Feinberg, John F Marshall
1Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, United States. sjodell@uci.edu
Abstract:
Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" regimen damages forebrain monoaminergic nerve terminals and produces subsequent cognitive deficits. Here we investigate performance on a social odor-based task, demonstrating enduring mAMPH-induced deficits in recognition memory. Three weeks after a neurotoxic mAMPH regimen, singly-housed male Long-Evans rats had four wooden beads placed in their home cage: three beads containing odors from their home cage (HC beads) and one bead from a cage of a rat not present in the colony room (N1 bead). Exploration times for each bead were recorded during three 1-min habituation trials separated by 1-min intertrial intervals. Twenty-four hours later, a 1-min memory test was conducted, in which animals were presented with two HC beads, one N1 bead, and one bead from another novel animal (N2). Saline- and mAMPH-treated rats showed similar, progressive decreases in exploration time for the N1 bead during the habituation trials, indicating equivalent short-term olfactory habituation to the novel odor. By contrast, during the subsequent memory test, saline-treated rats showed a strong preference for the N2 bead over the N1 bead while mAMPH-treated rats showed no preference. The use of the rats' primary sensory modality (olfaction) coupled with the social significance (from conspecifics) of the odors produces strong, long-lasting memories. Our results show that prior treatment with a neurotoxic regimen of mAMPH impairs long-term memory for the previously experienced odors. As compared with previously employed object recognition tasks, this test may be advantageous for investigating mAMPH-induced memory impairments in rodents.
Insights
Repeated methamphetamine (mAMPH) exposure causes long-term memory deficits in rats. This study shows mAMPH-treated rats fail to recognize familiar social odors, indicating impaired recognition memory.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Toxicology
Background:
- Repeated methamphetamine (mAMPH) administration in a binge pattern damages forebrain monoaminergic nerve terminals.
- This damage is associated with subsequent cognitive deficits, particularly in memory functions.
Purpose of the Study:
- To investigate the enduring effects of a neurotoxic mAMPH regimen on recognition memory in rats.
- To assess the utility of a social odor-based task for evaluating mAMPH-induced memory impairments.
Main Methods:
- Rats received either saline or a neurotoxic mAMPH regimen.
- Three weeks post-treatment, rats were habituated to familiar cage (HC) and novel odor (N1) beads.
- A memory test assessed preference for a novel odor (N2) over the familiar novel odor (N1).
Main Results:
- Both saline- and mAMPH-treated rats exhibited similar short-term olfactory habituation.
- Saline-treated rats showed a preference for the N2 bead, indicating recognition of the N1 odor.
- mAMPH-treated rats displayed no preference, failing to distinguish between N1 and N2 odors.
Conclusions:
- Neurotoxic methamphetamine exposure significantly impairs long-term olfactory recognition memory.
- Social odor-based tasks are sensitive to mAMPH-induced memory deficits.
- This paradigm may offer advantages over traditional object recognition tasks for studying mAMPH neurotoxicity.

