Methamphetamine Influences on Recognition Memory: Comparison of Escalating and Single-Day Dosing Regimens

Neuropsychopharmacology. 2008 May;33(6):1453-63. doi: 10.1038/sj.npp.1301510. Epub 2007 Jul 18.

Abstract

Methamphetamine (mAMPH) is an addictive drug that produces memory and recall impairments in humans. Animals subjected to a binge mAMPH dosing regimen that damages brain dopamine and serotonin terminals show impairments in an object recognition (OR) task. Earlier research demonstrated that preceding a single-day mAMPH binge regimen with several days of increasing mAMPH doses greatly attenuates its neurotoxicity in rats. The escalating dose (ED) paradigm appears to mimic the human pattern of escalating drug intake. The current aim was to test whether an ED plus binge mAMPH regimen produces OR impairments. In addition to its translational value, this experiment helps address whether monoaminergic neurotoxicity accounts for OR impairments seen after mAMPH administration. To further address this issue, a separate experiment investigated both OR impairments and monoamine transporter integrity in groups of rats treated with a range of mAMPH doses during a single day. An ED mAMPH regimen attenuated the acute hyperthermic response to the subsequent mAMPH binge and prevented the OR impairments and reductions in [125 I]RTI-55 binding to monoamine transporters in striatum, hippocampus (HC), and perirhinal cortex (pRh) that otherwise occur 1 week after the mAMPH binge. Single-day mAMPH regimens (4 x 1mg/kg to 4 x 4 mg/kg, s.c.) dose-dependently produced acute hyperthermia and, 1 week post-mAMPH, produced dose-dependent impairments in OR and reductions in monoamine transporter binding. The OR impairments of single-day mAMPH-treated rats correlated with monoaminergic transporter loss in ventral caudate-putamen, HC, and pRh. In aggregate, these findings suggest a correspondence between mAMPH-induced monoaminergic injury and the resulting OR deficits.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine-Related Disorders / psychology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects
  • Brain / anatomy & histology
  • Brain / drug effects
  • Brain / metabolism
  • Central Nervous System Stimulants / pharmacology*
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacokinetics
  • Conditioning, Operant / drug effects
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Methamphetamine / pharmacology*
  • Pattern Recognition, Visual / drug effects*
  • Pattern Recognition, Visual / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • Central Nervous System Stimulants
  • Dopamine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Methamphetamine
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine