Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats.
Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, i.p.) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, i.p.) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.
de Bruin
N M
NM
NICI/Department of Comparative and Physiological Psychology, University of Nijmegen, The Netherlands. debruin@nici.kun.nl
Ellenbroek
B A
BA
Cools
A R
AR
Coenen
A M
AM
van Luijtelaar
E L
EL
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012107:Research Design
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003913:Dextroamphetamine