title: Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex.
abstract: Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment.
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Michael D
authors: MD
authors: Scofield
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Heather
authors: H
authors: Trantham-Davidson
authors: Department of Psychology, University of Florida, Gainesville, FL, USA.
authors: Marek
authors: M
authors: Schwendt
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Kah-Chung
authors: KC
authors: Leong
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Jamie
authors: J
authors: Peters
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Ronald E
authors: RE
authors: See
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Carmela M
authors: CM
authors: Reichel
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003523:Cycloserine / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology; D008694:Methamphetamine / Q000008:administration & dosage*; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D012646:Self Administration; D046509:Tissue Culture Techniques
chemical_list: D000697:Central Nervous System Stimulants; D003523:Cycloserine; D018683:Excitatory Amino Acid Agents; D008694:Methamphetamine; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C109643:Ro 25-6981