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Neuropsychopharmacology. 2005 Nov;30(11):2026-34.

Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity.

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1Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.


Repeated moderate doses of methamphetamine (mAMPH) damage forebrain monoaminergic terminals and nonmonoaminergic cells in somatosensory cortex, and impair performance in a novelty preference task of object recognition (OR). This study aimed to determine whether the memory deficit seen after a neurotoxic mAMPH regimen results from damage to dopamine (DA) and/or serotonin (5-HT) terminals. Animals were given a neurotoxic regimen of mAMPH, p-chloroamphetamine (PCA, preferentially damages 5-HT terminals), d-amphetamine (d-AMPH, preferentially damages DA terminals), or saline. After 1 week, animals were trained and tested for OR memory. Rats treated with mAMPH showed no recognition memory during the short-term memory (STM) test, whereas both PCA- and d-AMPH-treated rats showed OR STM scores comparable to controls. After behavioral testing, the specificity of monoaminergic lesions was determined by postmortem [125I]RTI-55 binding to dopamine (DAT) and serotonin (SERT) transporter proteins. Tissue from a separate group of animals killed 3 days after drug treatment was processed for Fluoro-Jade (F-J) fluorescence histochemistry to detect damaged cortical neurons. mAMPH-treated rats showed reductions in striatal DAT and hippocampal (HC) and perirhinal (pRh) SERT, as well as degeneration of neurons in primary somatosensory cortex. In PCA-treated rats, HC and pRh SERT were substantially depleted, but striatal DAT and cortical neuron survival were unaffected. By contrast, d-AMPH-treated animals showed marked depletions in striatal DAT and cortical neurodegeneration, but HC and pRh SERT were unaffected. This pattern of results indicates that no single feature of mAMPH-induced neurotoxicity is sufficient to produce the OR impairments seen after mAMPH treatment.

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