title: Memantine improves memory impairment and depressive-like behavior induced by amphetamine withdrawal in rats.
abstract: Amphetamine (AMPH) induces deficits in cognition, and depressive-like behavior following withdrawal. The aim of the present study was to investigate whether pre-treatment with memantine (5mg/kg, i.p.), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, attenuates memory impairment induced by withdrawal from a 1 day binge regimen of AMPH (2mg/kg, four times every 2h, i.p.), in the novel object recognition test in rats. Herein, the influence of scopolamine (0.1mg/kg), an antagonist of the muscarinic cholinergic receptors, and the impact of MK-801 (0.1mg/kg), an antagonist of the NMDA receptors, on the memantine effect, were ascertained. Furthermore, the impact of memantine (5; 10; 20mg/kg, i.p.) was measured on depression-like effects of abstinence, 14 days after the last AMPH treatment (2mg/kg×1×14 days), in the forced swim test. In this test, the efficacy of memantine was compared to that of tricyclic antidepressant imipramine (10; 20; 30mg/kg, i.p.). Our study indicated that withdrawal from a binge regimen of AMPH impaired recognition memory. This effect was attenuated by administration of memantine at both 72h and 7 days of withdrawal. Moreover, prior administration of scopolamine, but not MK-801, decreased the memantine-induced recognition memory improvement. In addition, memantine reversed the AMPH-induced depressive-like behavior in the forced swim test in rats. The antidepressant-like effects of memantine were stronger than those of imipramine. Our study indicates that memantine constitutes a useful approach towards preventing cognitive deficits induced by withdrawal from an AMPH binge regimen and by depressive-like behavior during AMPH abstinence.
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Marszalek-Grabska
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Gibula-Bruzda
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jenda
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Gawel
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland. Electronic address: jolka.kotlinska@umlub.pl.
authors.forename: J H
authors.initials: JH
authors.lastname: Kotlinska
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000661:Amphetamine; D012601:Scopolamine; D007099:Imipramine; D008559:Memantine
keywords: Amphetamine withdrawal; Forced swim test; Memantine; Novel object recognition test; Rats