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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Neurotoxic methamphetamine regimen severely impairs recognition memory in rats
Nadja Schröder1, Steven J O'Dell, John F Marshall
1Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
Abstract:
Methamphetamine (mAMPH), when administered repeatedly to rodents or primates, is neurotoxic to some cortical neurons and to forebrain dopaminergic and serotonergic axon terminals. The aim of the present study was to investigate the effects of a neurotoxic regimen of mAMPH on two hippocampus-dependent memory tasks: object recognition, a nonspatial memory task, and the Morris water maze, a spatial memory task. Male rats were treated with mAMPH (4 x 4.0 mg/kg, s.c.) or saline and trained in the object recognition task 1 week and 3 weeks later. During training, animals explored two identical copies of the same object. In retention test sessions one of the objects was replaced by a novel object. mAMPH-treated rats showed no recognition memory during the short-term memory (STM) test, given 90 min after the training session, and showed marked impairments in the long-term memory (LTM) test, given 24 h after training. Even 3 weeks after drug injections, the mAMPH-treated animals were unable to discriminate between the novel and familiar objects during both STM and LTM tests. Despite the severe deficits observed in the recognition memory, no effects of prior mAMPH treatment were seen in the water maze task. Damage to monoamine terminals was confirmed by significant 30-40% losses of [(125)I]RTI-55 binding to striatal dopamine transporter and hippocampal serotonin transporter sites at both 1 and 3 weeks after mAMPH treatments. Thus, administration of mAMPH restricted to a single day can produce a profound, persistent, and selective deficit in a nonspatial hippocampus-dependent memory.
Insights
Single-day methamphetamine (mAMPH) exposure causes persistent memory deficits in rats, specifically impairing nonspatial recognition memory. This neurotoxic effect on memory persists for at least three weeks post-treatment.
Area of Science:
- Neuroscience
- Psychopharmacology
- Memory Research
Background:
- Methamphetamine (mAMPH) is known to be neurotoxic, particularly to dopaminergic and serotonergic axon terminals.
- Previous studies indicate mAMPH affects neuronal structures, but its specific impact on hippocampus-dependent memory requires further investigation.
Purpose of the Study:
- To investigate the effects of a neurotoxic mAMPH regimen on object recognition and Morris water maze tasks.
- To determine if mAMPH-induced neurotoxicity selectively impairs nonspatial hippocampus-dependent memory.
Main Methods:
- Rats received a single-day regimen of mAMPH (4 x 4.0 mg/kg) or saline.
- Animals were trained and tested on object recognition (short-term and long-term memory) 1 and 3 weeks post-treatment.
- Morris water maze task was also administered to assess spatial memory.
Main Results:
- mAMPH-treated rats exhibited significant deficits in both short-term and long-term object recognition memory.
- These recognition memory impairments persisted for at least 3 weeks after mAMPH administration.
- No significant effects of mAMPH treatment were observed in the Morris water maze spatial memory task.
- Confirmed neurotoxicity through a 30-40% loss of dopamine and serotonin transporter binding sites.
Conclusions:
- A single day of mAMPH administration induces profound, persistent, and selective deficits in nonspatial hippocampus-dependent memory.
- The findings highlight the vulnerability of specific memory systems to mAMPH neurotoxicity.
- Object recognition memory is particularly susceptible to mAMPH-induced damage, while spatial memory remains unaffected.
