Juvenile exposure to ketamine causes delayed emergence of EEG abnormalities during adulthood in mice

Drug Alcohol Depend. 2014 Jan 1:134:123-127. doi: 10.1016/j.drugalcdep.2013.09.017. Epub 2013 Sep 27.

Abstract

Background: Increased susceptibility to cognitive impairment or psychosis in adulthood is associated with adolescent drug abuse. Studies in adults have identified impairments in attention and memory, and changes in EEG, as common consequences of ketamine abuse. In contrast, the effects of ketamine on the juvenile brain have not been extensively tested. This is a significant omission, since abuse of ketamine is often observed within this age group.

Objectives: Juvenile mice (4-6 weeks of age) were administered ketamine (20mg/kg) for 14 days. EEG was assessed in response to auditory stimulation both at one week following ketamine exposure at 7 weeks of age (juvenile) and again at 12 weeks of age (adult). EEG was analyzed for baseline activity, event-related power and event-related potentials (ERPs).

Results: While no effects of ketamine exposure were observed during the juvenile period, significant reductions in amplitude of the P20 ERP component and event-related gamma power were seen following ketamine when re-tested as adults. In contrast, reductions in event-related theta were seen in ketamine-exposed mice at both time points.

Conclusions: Age related deficits in electrophysiological components such as P20 or event-related gamma may be due to an interruption of normal neural maturation. Reduction of NMDAR signaling during adolescence leads to delayed-onset disruption of gamma oscillations and the P20 component of the ERP. Further, delayed onset of impairment following adolescent ketamine abuse suggests that methods could be developed to detect and treat the early effects of drug exposure prior to the onset of disability.

Keywords: Drug-abuse; Gamma; NMDA; Oscillations; Schizophrenia; Theta.

Publication types

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

MeSH terms

  • Acoustic Stimulation / methods
  • Age Factors
  • Animals
  • Electrodes, Implanted
  • Electroencephalography / drug effects*
  • Electroencephalography / methods
  • Evoked Potentials, Auditory / drug effects
  • Evoked Potentials, Auditory / physiology
  • Ketamine / administration & dosage
  • Ketamine / toxicity*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Reaction Time / drug effects*
  • Reaction Time / physiology

Substances

  • Ketamine