Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity.
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.
Belcher
Annabelle M
AM
1Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
O'Dell
Steven J
SJ
Marshall
John F
JF
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003913:Dextroamphetamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005452:Fluoresceins; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D008694:Methamphetamine; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009483:Neuropsychological Tests; D009930:Organic Chemicals / Q000378:metabolism; D010296:Parietal Lobe / Q000166:cytology / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005452:Fluoresceins; D009930:Organic Chemicals; D019275:Radiopharmaceuticals; D018490:Serotonin Agents; C435731:fluoro jade; D012701:Serotonin; D008694:Methamphetamine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D010133:p-Chloroamphetamine; D003042:Cocaine; D003913:Dextroamphetamine