Behavioral and electrophysiological comparison of ketamine with dizocilpine in the rat

We have compared the effects of MK 801 and ketamine on a measure of anesthesia (loss of righting reflex) and two measures of basal ganglia dopamine (DA) function: apomorphine (APO)-induced stereotypy and APO-induced excitation of type II globus pallidus (GP) neurons. As expected, ketamine induced anesthesia. High-dose MK 801 administered IP induced ataxia, but not anesthesia. When administered i.v., high-dose MK 801 induced anesthesia in only three of five rats. Using a modified stereotypy scale, it was found that pretreatment with MK 801 blocked APO-induced stereotypic sniffing. Intravenous ketamine also blocked APO-induced stereotypy, but IP ketamine did not. Similar results were observed in neurophysiological studies; MK 801 altered the excitation of type II GP neurons by APO. Intravenous ketamine (5 mg/kg) also altered the responsiveness of these cells to APO, but ketamine anesthesia (150 mg/kg, IP) had no effect. These findings suggest that MK 801 is not an effective anesthetic in rats, and the method of administration of ketamine plays a role in its ability to exert NMDA receptor blockade.