Comparative electroencephalographic and behavioral effects of phencyclidine, (+)-SKF-10,047 and MK-801 in rats.
Female Sprague-Dawley rats prepared with chronic i.v. cannulas and/or cerebrocortical electrodes were administered sequentially increasing doses of phencyclidine (PCP, 0.1-6.4 mg/kg/injection), (+)-SKF-10,047 [(+)-N-allynormetazocine] (0.4-25.6 mg/kg/injection) or MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate] (0.01-0.64 mg/kg/injection). Effects on overt behavior, cortical EEG power spectra, locomotor activity and rotarod performance were assessed. Quantitative EEG spectral parameters (peak, mean and edge frequency; total and relative power; time domain descriptors mobility and complexity) were analyzed from the global frequency range of 1 to 50 Hz. Increasing doses of each drug produced increases in EEG spectra power from 1 to 50 Hz which was associated with a slowing of the peak frequency. PCP and MK-801 produced decreases in the mean frequency, mobility and edge frequency whereas (+)-SKF-10,047 produced increases in these spectral parameters. Moreover, (+)-SKF-10,047 increased complexity whereas MK-801 decreased complexity and PCP did not change this parameter. Total spectral power from 20 to 50 Hz was increased by (+)-SKF-10,047 and PCP, but was not changed by MK-801. Each drug increased spontaneous locomotor activity. At the highest doses, PCP and MK-801 decreased activity whereas (+)-SKF-10,047 was lethal. Each drug disrupted rotarod performance. The rank order of potency for each effect was: MK-801 greater than PCP greater than (+)-SKF-10,047. The data indicate that subtle differences in the effects of these drugs can be detected using EEG power spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Marquis
K L
KL
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore.
Paquette
N C
NC
Gussio
R P
RP
Moreton
J E
JE
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004569:Electroencephalography; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D017480:Receptors, sigma; D013239:Stereotyped Behavior / Q000187:drug effects
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine