title: Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl-D-aspartate receptor expression.
abstract: BACKGROUND
  Chronic methamphetamine (meth) abuse in humans can lead to various cognitive deficits, including memory loss. We previously showed that chronic meth self-administration impairs memory for objects relative to their location and surrounding objects. Here, we demonstrate that the cognitive enhancer, modafinil, reversed this cognitive impairment independent of glutamate N-methyl-d-aspartate (GluN) receptor expression
  
  
  METHODS
  Male, Long-Evans rats underwent a noncontingent (Experiment 1) or contingent (Experiment 2) meth regimen. After one week of abstinence, rats were tested for object-in-place recognition memory. Half the rats received either vehicle or modafinil (100mg/kg) immediately after object familiarization. Rats (Experiment 2) were sacrificed immediately after the test and brain areas that comprise the key circuitry for object in place performance were manually dissected. Subsequently, glutamate receptor expression was measured from a crude membrane fraction using Western blot procedures.
  
  
  RESULTS
  Saline-treated rats spent more time interacting with the objects in changed locations, while meth-treated rats distributed their time equally among all objects. Meth-treated rats that received modafinil showed a reversal in the deficit, whereby they spent more time exploring the objects in the new locations. GluN2B receptor subtype was decreased in the perirhinal cortex, yet remained unaffected in the prefrontal cortex and hippocampus of meth rats. This meth-induced down regulation occurred whether or not meth experienced rats received vehicle or modafinil.
  
  
  CONCLUSIONS
  These data support the use of modafinil for memory impairment in meth addiction. Further studies are needed to elucidate the neural mechanisms of modafinil reversal of cognitive impairments.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: reichel@musc.edu.
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Meghin G
authors.initials: MG
authors.lastname: Gilstrap
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Ramsey
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008694:Methamphetamine / Q000633:toxicity*; D000077408:Modafinil; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*
chemical_list: D001559:Benzhydryl Compounds; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D008694:Methamphetamine; D000077408:Modafinil
keywords: Glutamate; Memory; Methamphetamine; Object recognition; Perirhinal cortex; Self-administration