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.
Kelland
M D
MD
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Soltis
R P
RP
Boldry
R C
RC
Walters
J R
JR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D010879:Piperazines; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D001058:Apomorphine