Neurotoxic methamphetamine regimen severely impairs recognition memory in rats
Version of Record online: 23 APR 2003
Copyright © 2003 Wiley-Liss, Inc.
Volume 49, Issue 2, pages 89–96, August 2003
How to Cite
Schröder, N., O'Dell, S. J. and Marshall, J. F. (2003), Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse, 49: 89–96. doi: 10.1002/syn.10210
- Issue online: 23 APR 2003
- Version of Record online: 23 APR 2003
- Manuscript Accepted: 21 FEB 2003
- Manuscript Received: 11 NOV 2002
- PHS. Grant Number: DA 12204
- water maze;
- object recognition;
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 × 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 [125I]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. Synapse 49:89–96, 2003. © 2003 Wiley-Liss, Inc.