Modafinil restores methamphetamine induced object-in-place memory deficits in rats independent of glutamate N-methyl-D-aspartate receptor expression

作者：Reichel Carmela M^*; Gilstrap Meghin G; Ramsey Lauren A; See Ronald E

来源：Drug and Alcohol Dependence, 2014, 134: 115-122.

DOI：10.1016/j.drugalcdep.2013.09.018

• Glutamate
• Memory
• Methamphetamine
• Perirhinal cortex
• Self-administration
• Object recognition

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 (100 mg/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 methtreated 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. G1uN2B 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.

• 出版日期2014-1-1