Comparison of the effects of pretreatment with competitive or noncompetitive NMDA antagonists on vestibular...

Unilateral labyrinthectomy (UL) results in a syndrome of ocular motor and postural disorders which abates over time in a process of behavioural recovery known as vestibular compensation. We have previously reported that a single systemic pre-UL injection of the organic Ca2+ channel antagonist verapamil or the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 reduces the behavioural effects of UL in guinea pigs. The present study was conducted to determine if similar effects would be obtained with single injections of the competitive NMDA receptor antagonists 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) or cis-4-(phosphonomethyl)-piperidine-2-carboxylic acid (CGS 19755). Guinea pigs received an IP injection of 5 mg/kg CPP 2.5 h pre-UL, 5 or 10 mg/kg CPP 1 h pre-UL, 10 or 20 mg/kg CGS 19755 1 h pre-UL, or 1 ml/kg vehicle (saline) 1 h pre-UL, and the effects on the compensation of spontaneous nystagmus were measured over the following 52 h post-UL. Pretreatment with CPP had no significant effect on spontaneous nystagmus frequency or its compensation over 52 h post-UL. However, pretreatment with CGS 19755 resulted in a significant decrease in spontaneous nystagmus frequency without any acceleration of the rate of compensation.